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Year 2 > Intrathoracic Malignancy > Flashcards

Intrathoracic Malignancy Flashcards

1
Q

What is the leading cause of cancer mortality?

A

Lung cancer

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2
Q

What is the relative risk of passive smoking?

A

1.25, equivalent to 1 cigarette per day.

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3
Q

What is the major cause of lung cancer?

A

Smoking
-> Makes up almost all of total cases in over 40s. Increases risk of lung cancer with duration and amount of cigarettes, with reduced risk after cessation. It is a synergistic and additive effect to other lung cancer risk factors.

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4
Q

What are the carcinogenic substances in cigarette smoke?

A

Most potent are:
polycyclic aromatic hydrocarbons
Polonium 210
Tobacco specific nitrosamines

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5
Q

What are causes of lung carcinomas other than smoking?

A

Occupational exposure to carcinogens such as asbestos, radon, arsenic, polycyclic aromatic hydrocarbons
Environmental radon
Chronic lung diseases such as pulmonary fibrosis and COPD
Air pollution

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6
Q

What is radon?

A

Radioactive iodine gas which once inhaled, emits alpha particles which causes damage to the lung cells. Air crew, nuclear power station workers and those living in Cornwall are at a high risk of radon exposure.

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7
Q

What is the general development of lung cancer?

A

Carcinogenic substances cause chronic inflammation, hyperplasia or metaplasia which cause genetic lesions accumulate and result in stepwise progression of excessive growth, local invasiveness and ability of tumour cells to metastases.

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8
Q

Which type of mutations are important for tumour survival?

A

Driver mutations: mutations that provide selective growth advantages for normal cells to become cancer cells to increase tumour size and metastasis. These include proto-oncogenes which drive cell proliferation and mutations to tumour suppressor genes.

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9
Q

What are the symptoms of lung cancer?

A

Shortness of breath, chronic cough, chest pain and hoarseness.
Increased sputum production and volume. Angiogenesis by the tumour results in blood vessels rupturing and causing haemoptysis.
Paraneoplastic syndrome.

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10
Q

What happens when a lung tumour obstructs the airways?

A

Reduced airflow causes dyspnoea and triggers the cough reflex. Increased angiogenesis results in haemoptysis.

Lobar collapse due to bronchial obstruction because of decreased airflow.

Pneumonia and lung absecess because microorganisms do not efficiently leave the airways via breathing or coughing, increasing infection risk.

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11
Q

What happens when a tumour spreads to the pleura?

A

Pleural effusion where fluid collects in the space between the lungs and pleura. This causes dyspnoea and chest pain.

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12
Q

What happens when a tumour spreads to the recurrent laryngeal nerve?

A

Hoarseness of voice.

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13
Q

Why does dysphagia occur in lung cancer?

A

Oesophageal invasion by tumour.

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14
Q

How can lung cancer affect the chest cavity?

A

Causes rib destruction and diaphragm paralysis and pericarditis.

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15
Q

What is a pancoast tumour?

A

Lung cancer at the apex of the lung which result in compression of:

Recurrent laryngeal nerve, causing hoarse voice.

Superior cervical ganglion resulting in Ipsilateral Horner’s syndrome

Upper brachial plexus causing shoulder pain and weakness

Superior vena cava, resulting in SVC syndrome.

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16
Q

What is Superior Vena Cava syndrome?

A

Typically caused by a small cell or squamous cell carcinoma of the lung apex, called a pancoast tumour. This results in obstruction to venous return from the head and neck to the right atrium resulting in:
Facial and neck oedema
Veins open and become visibly dissented on the chest
Capillaries pool with blood and leak to surrounding tissue, causing cough and dyspnoea.
It reduces blood returning to the heart and results in hypotension, tachycardia and tachypnoea.

Symptoms worsen when the patient raises their arms above their heads.

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17
Q

What is paraneoplastic syndrome?

A

Occurs in small cell carcinoma, where there is cancer of the neuroendocrine cells, that affect sites distal to the tumour and resulting in overproduction of:

ACTH = Cushing syndrome
ADH= Water retention and hypertension
Parathyroid like hormone= osteoporosis
Gonadotropin= gynaecomastia (enlargement of breasts)

It also causes Lambert-Eaton myasthenic syndrome.

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18
Q

What is Lambort-Eaton myasthenic syndrome?

A

Immune response against the voltage gated Ca2+ channels of presynaptic neurons in the neuromuscular junction, inhibiting acetylcholine release and results in proximal muscle weakness which improves with exercise.

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19
Q

What is Troussaeu’s syndrome?

A

Blood clotting disorder called migratory thrombophlebitis which is inflammation of the vein due to a blood clot that occurs in cancer malignancy due to tumour cells inducing thrombin activation. It causes:
Acanthosis nigiricans: dark brown velvety lesion
This tends to occur in adenocarcinomas of the lung.

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20
Q

What are the imaging techniques for lung carcinoma?

A

X-ray
CT scan
PET scan
Bronchoscopy
MRI

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21
Q

How is a lung carcinoma diagnosed?

A

Cytology of the sputum
Bronchoscopy
Surgical methods such as lobotomy and pneumoectomy.

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22
Q

What are the general types of lung cancer classifications?

A

Primary lung cancer
Benign
Metastatic
Malignant

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23
Q

What are the types of primary lung cancers?

A

Epithelial
Mesenchymal
Lymphoid

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24
Q

What are the categories of lung cancer by histology?

A

Small cell carcinoma
Non-small cell carcinoma

25
Q

What is are the types of non-small cell carcinoma?

A

Adenocarcinoma
Squamous cell carcinoma
Large cell carcinoma

26
Q

What is the more common lung cancer by general histology?

A

Non-small cell carcinoma.

27
Q

What is the most common non-small cell carcinoma?

A

Adenocarcinoma is most common in non-smokers but has a strong association with tobacco use.

These affect the alveolar type 2 cells and glands of the bronchi and peripheral lung tissue due to driver mutations. It causes abnormal mucin production by affecting the acinar, glandular or papillar structures of the columnar epithelia. It is undetectable by imaging. And causes trousseau’s syndrome.

28
Q

What are squamous cell carcinoma?

A

Type of non-small cell carcinoma which typically affects the large airways and causes excessive growth via dysplasia, where the cuboidal/columnar epithelia -> squamous epithelia, resulting in pleomorphic and hyper chromatic nuclei with intercellular bridges and poor keratinisation.

29
Q

What is a large cell carcinoma?

A

Least common type of lung cancer, which is a non-small cell carcinoma of undifferentiated cancer cells that are typically large, diagnosed via exclusion of other histological lung cancer types. It typically occurs in the proximal hilum or peripheral lung tissues. It can have squamous and glandular features.

30
Q

What are the features of small cell carcinomas?

A

Forms neuroendocrine tumours which result in paraneoplastic syndrome and commonly metastasis occurs. The histological features are small neuroendocrine cells that are crowded and contain hyperchromatic nuclei, little cyptoplasm. These tumours arise from cells with a high amine content and uptake and high content of decarboxylase enzyme.

31
Q

What are pleomorphic nuclei?

A

Varying size and shape of nuclei.

32
Q

What are hyperchromatic nuclei?

A

Nuclei which stains more deeply.

33
Q

Where do squamous cell carcinomas occur?

A

It occurs centrally in the lungs and affects the large airways. It has the strongest association with smoking of all the non-small cell carcinomas and has a worse prognosis. It also commonly causes cavitations lesions.

34
Q

What are the therapies available for lung cancer?

A

Choice of treatment depends on histological subtype and TNM staging:
Surgery
Radiotherapy
Chemotherapy
Immunotherapies

35
Q

What is the treatment and prognosis of small cell carcinomas?

A

It is the most likely to have metastasis occur and is the most aggressive form of lung cancer. Biggest risk factor is smoking.

Early stage treatment: Radical (curative) radiotherapy and chemotherapy which has a 5 year survival rate of 20%.

Late stage treatment: Pallaitve chemotherapy and radiotherapy which has a survival time of 9 months.

36
Q

What is the treatment and prognosis of non-small cell carcinomas?

A

Early TNM stage in 1-2: Surgical resection is the first point of treatment with a 5 year survival rate of 25-60%. Radial radiotherapy is an alternative option.

Late TNM stage in 3-4: palliative chemotherapy and radiotherapy with a five year survival rate of 1%>

37
Q

What are the drug therapies for non-small cell carcinomas?

A

Tyrosine kinase inhibitors
ALK inhibitors
ROS1 inhibitors

38
Q

How can lung cancer be diagnosed on a molecular level?

A

Histopathology
PD-L1 testing of cancer cells
Gene mutations such as ROS-1, RET and NRK fusion.

39
Q

What are primary intrathoracic malignancies?

A

Cancer of the organs within the thorax:
Lung cancer
Malignant mesothelemia.

40
Q

What is malignant mesothelemia?

A

Cancer of the mesothelium with the lining of the body cavities, and in the lungs this affects the visceral and parietal pleura, increasing calciretinin expression. The greatest risk factor is asbestos exposure which causes chronic inflammation and results in the formation of plaques on the hyaline of the lung pleura. It occurs due to a mutation of the NF2 tumour repressor gene and BAP1 gene.

41
Q

What are the clinical features of malignant mesothelemia?

A

Due to the site of the pleural tumour, causes pleural effusion and pleurisy
Shortness of breath, cough, fullness in chest, fever
Metastatic spread to the hilar lymph nodes.

Typically affects older adults, and men due to occupational exposure from asbestos.

42
Q

How is malignant mesothelemia diagnosed?

A

Biopsy of the tumour
X ray, CT scans, MRI
Thickening of the pleura indicates effusion
Pleural biopsy
Thoracoscopy: procedure to look inside the lungs

43
Q

What are the histological types of malignant mesothelemia?

A

Primary malignant mesothelemia which consists of mesothelial, Mesenchymal and lymphoproliferative disorders

Malignant

Metastatic

44
Q

What are the types of malignant mesothelemia?

A

Tumour arising from the mesothelium of the epithelial cell layer:
Epithelioid which is the most common
Sarcamoid
Biphasic

45
Q

What does the TNM system stand for?

A

Tumour size from 0-4
Node involvement from 0-3
Metastasis from 0-1

46
Q

What is the role of EGFR-TK?

A

Blocks activity of epidermal growth factor receptor for signal transduction by tyrosine kinase for ell proliferation in non-small cell carcinoma.

47
Q

What is the role of ALK?

A

Alkaline phosphatase is a transmembrane tyrosine kinase receptor for signal transduction to nucleus for cell proliferation of tumours in non-small cell carcinoma.

48
Q

What is the role of ROS1?

A

Proto-oncogene for tyrosine kinase that undergoes genetic rearrangement of bases to drive tumour growth in non-small cell carcinoma.

49
Q

What is NRK?

A

Nik-related protein kinase which encodes for tyrosine kinase activation.

50
Q

What is the role of BAP1 gene?

A

BAP1 is a tumour suppressor gene encoding for ubiquitin C-terminal hydrolyse that regulates protein synthesis and cellular differentiation.

51
Q

What is the treatment for malignant mesothelemia?

A

Pleurodesis: obliteration of the pleural space by adhering the visceral pleural to the parietal pleural to prevent pleural effusions and pneumothorax.
Pneumonectomy and pleuronectomy however curative resection may not be possible because it can be a diffuse condition
Radiotherapy and Chemotherapy
Immunotherapy treatment with checkpoint inhibitors

-> there is a poor prognosis of 20% survival

52
Q

What is secondary intrathoracic malignancy?

A

Malignancy due to metastases where the lungs and pleura are common sites for this to occur. Generally occurs due to Breast and GI and ovarian cancer.

53
Q

Which occupations increase asbestos exposure?

A

Demolition workers
Boiler installers
Carpenters
Electricians

54
Q

What are asbestos?

A

Silicate materials used in insulation with cumulative exposure from indestructible fibres. It induces chronic inflammation and fibrosis in the lungs which increase the risk of carcinomas of the lung and mesothelium.

55
Q

What are the types of asbestos?

A

Serpentine
Amphiboles
-> These become coated with protein and iron to form asbestos bodies.

56
Q

Which type of asbestos cause cancer?

A

Serpentine long curly fibres. It is the most common type of asbestos which causes mesothelioma and lung cancer.

57
Q

What is amphibioles?

A

Straight rigid fibres which are important for mesothelioma development

58
Q

Where are the common sites of lung cancer metastases?

A

Brain
Liver
Adrenal glands
Bone

59
Q

What are the features of paraneoplastic syndrome?

A

Increased production of:
PTH causing osteoporosis
ADH
Cortisol, causing water retention

Year 2 (247 decks)

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