Pathology of Lung Cancer Flashcards
What is the most common cause of cancer-related death?
Lung cancer
What is the leading cause of lung cancer?
tobacco (smoking)
What is the second most common cause of lung cancer?
asbestos
What are some other causes of cancer apart from tobacco and asbestos?
(5)
- Environmental radon
- Other occupational exposure
(e. g. Chromates, Hydrocarbons, Nickel) - Air pollution and Urban environment
- Other radiation
- Pulmonary fibrosis
How does smoking increase the risk of developing lung cancer, for males and females?
Who may be more susceptible? Explain this.
males: x22
females: x12
Females - may have something to do with inhalation and pack years.
How is pack years calculated?
No. smoked / pack / day / per
What are the two important groups of compounds in cigarettes that are thought to cause lung cancer?
- polycyclic aromatic hydrocarbons (10)
- N-nitrosamines (7)
What type of lung cancer are the N-nitrosamines thought to cause?
adenocarcinomas in the periphery of the lungs
What type of lung cancer are the polycyclic aromatic hydrocarbons thought to cause?
squamous cell carcinoma
What is an adenocarcinoma?
a malignant tumour formed from glandular structures in epithelial tissue.
What are the two main pathways of carcinogenesis in the lung i.e. which areas of lung?
- lung periphery
- central lung airways
In the lung periphery and central lung airways, describe cells transform and which type of cancer develops.
(4)
lung periphery:
- bronchiolalveolar epithelial stem cells transform
- develops adenocarcinoma
central lung airways:
- bronchial epithelial stem cells transform
- develops squamous cell carcinoma
Bronchioloalveolar carcinoma (BAC) is a relatively rare _________ that typically arises in the ______ ______ and grows along alveolar walls, without destroying the lung parenchyma.
adenocarcinoma
lung periphery
______ _______ ______ is more strongly associated with smoking than any other type of non-small cell lung cancer.
squamous cell carcinoma
___________________ usually occur in the central part of the lung or in one of the main airways (left or right bronchus).
Squamous cell lung tumors
What is squamous dysplasia?
Squamous dysplasia is defined as altered epithelium with an increased likelihood for progression to squamous cell carcinoma.
What is an adenoma?
a benign tumour formed from glandular structures in epithelial tissue.
What is a carcinoma?
3
- start in epithelial tissues.
- these cover the outside of the body as the skin.
- there are different types of epithelial cells and these can develop into different types of carcinoma.
What is a squamous cell carcinoma?
2
- starts in squamous cells.
- the flat, surface covering cells found in areas such as the skin or the lining of the trachea, bronchi or oesophagus.
What is an adenocarcinoma?
2
- start in glandular cells called adenomatous cells.
- glandular cells produce fluids to keep tissues moist.
Would the developmental process of an invasive bronchogenic carcinoma be more associated with non-smokers or smokers?
Process strongly associated with smoking.
What is different about peripheral lung adenocarcinogenesis compared with a given squamous cell carcinoma affecting the bronchus?
(2)
- The process of peripheral lung adenocarcinogenesis is less strongly but still associated with smoking compared to a SC carcinoma, which is heavily influenced by smoking.
- The sequence of peripheral lung adenocarcinogenesis occurs in non-smokers also.
What is the multi-hit theory of carcinogenesis in lung cancer?
(2)
- about 3-6 hits are required before a cancer forms.
- these mutations to important genes must be in the correct sequence also.
How might genetics affect the likelihood of cancer forming?
- people may have polymorphisms that allow them to metabolise pro-carcinogens.
- some people are more predisposed to higher nicotine addiction.
What sort of cells are the target for carcinogens?
stem cells
Which type of lung cancer is usually found in non-smokers?
peripheral lung adenocarcinoma
Outline a typical adenoma – carcinoma sequence for a peripheral lung adenocarcinoma.
(3)
- atypical adenomatous hyperplasia (benign)
- adenocarcinoma in situ
- invasive adenocarcinoma (malignant)
What is oncogene addiction?
- the phenomenon in which some cancers remain dependent on one or a few genes for both maintenance and cell survival.
What is an addictive oncogene?
- an oncogene that once inactivated will inhibit the future growth of the cancer.
What is important about addictive oncogenes in terms of treatment?
(2)
- molecular target therapy
- gene inactivation prevents cancer spread.
What is the most common key driver mutation in lung cancer?
KRAS (35%)
Name a key driver mutation which is smoking induced.
KRAS
Which driver mutations are not smoking induced?
i.e. not related to tobacco carcinogenesis
(5)
EGFR BRAF HER2 ALK rearrangements ROS1 gene rearrangements
Which four driver mutation targets have approved treatment agents for adenocarcinomas from the FDA?
EGFR mutation
ALK rearrangement
ROS1 rearrangement
BRAF mutation
Give an example of a cause of a benign mass lesion in the lung?
pneumonia
Outline some examples of some tumours in the lung which aren’t lung cancer.
i.e. they may be benign, or a cancer of another origin.
- carcinoid tumour
- tumour of bronchial glands
- lymphoma
- sarcoma
- metastases
Why are metastases so common in the lung?
- all blood must pass through the lungs
- cancer can metastasise easily through blood
What are the 4 main types of lung cancer?
i.e. the most common accounting for >90% of cases.
- squamous cell (40%)
- adenocarcinoma (41%)
- small cell carcinoma (15%)
- large cell carcinoma (4%)
Histologically, what types of lung cancer are grouped together as non-small cell carcinomas (NSCLC)?
(4)
- adenocarcinoma
- squamous cell carcinoma
- large cell carcinoma
- others
By the time that lung cancer presents symptomatically, is it possible to be treated completely?
- Lung cancer presents late in its natural history.
- generally speaking, symptomatic lung cancer is fatal.
What are the local effects of lung cancer in terms of bronchial obstruction?
(4)
- collapse
- endogenous lipoid pneumonia
- infection/abscess
- bronchiectasis
What is endogenous lipoid pneumonia?
- obstruction of the airway resulting in the accumulation of cellular breakdown debris, including cholesterol from destroyed alveolar cell walls.
- these lipids are difficult to digest and the macrophages, which attempt to phagocytose them, accumulate within the alveolar spaces.
What are the local effects of lung cancer in terms of the pleurae?
(2)
- inflammation of the pleura (pleurisy)
- malignant spread to the pleura
What are the local effects of lung cancer in terms of direct invasion?
- invasion of the chest wall
- invasion of the mediastinum (SVC, pericardium)
- invasion of nerves ( phrenic, left recurrent laryngeal, brachial plexus, cervical sympathetic)
If lung cancer spreads to the phrenic nerve, what happens?
paralysis of diaphragm
If lung cancer spreads to the left recurrent laryngeal nerve, what happens?
(2)
- innervation of voice box affected
- hoarseness
- bovine cough
If lung cancer spreads to the brachial plexus, what happens?
2
- pancoast T1 damage
- pain and weakness in the muscles of the arm and hand
If lung cancer spreads to the cervical sympathetic nerve, what happens?
How does this present?
(4)
- Horner’s syndrome:
- constriction of one eye
- loss of sweating on one side of the face
- dropping of one eyelid
What are the effects of a lung cancer on lymph nodes?
2
- mass effect, many lymph nodes become cancerous
- lymphangitis carcinomatosa: interstitial cancer of lymph affecting drainage of lungs
What are the common distant metastases in lung cancer?
5
Liver Adrenals Bone Brain Skin
Outline some of the skeletal non-Metastatic paraneoplastic effects of lung cancer.
(2)
- finger clubbing
- HPOA inflammation
Outline some of the endocrinal non-Metastatic paraneoplastic effects of lung cancer.
(3)
- ACTH, SIADH, PTH
- Carcinoid syndrome
- Gynecomastia
Outline some of the neurological non-Metastatic paraneoplastic effects of lung cancer.
(4)
- Polyneuropathy
- Encephalopathy
- Cerebellar degeneration
- Myasthenia
Outline some of the cardiovascular non-Metastatic paraneoplastic effects of lung cancer.
(1)
- Migratory thrombophlebitis
Outline some of the renal non-Metastatic paraneoplastic effects of lung cancer.
(1)
- nephrotic syndrome: passing too much protein in your urine.
Which abnormal hormone productions are a likely cause of small cell carcinoma?
(2)
- ACTH
- siADH
Which abnormal hormone productions are a likely cause of squamous (non small) cell carcinoma?
(1)
PTH
What are some investigations carried out to diagnose lung cancer?
(7)
- CXR
- sputum cytology (rare)
- bronchoscopy
- trans-thoracic fine needle aspiration
- trans-thoracic core biopsy
- pleural effusion cytology/biopsy
- advanced imaging techniques (CT, MRI, PET)
What factors determines the prognosis of Lung cancer?
3
- Staging of cancer
- classification of type
- markers, oncogenes, gene expression profile
What is the 5 year survival rate in patients with operable stage I and stage II lung cancer?
Stage I = >60%
Stage II = 35%
Which type of lung cancer has the poorest prognosis?
small cell carcinoma
What will help select a patient’s therapy after a diagnosis has been made?
predictive biomarkers
Which predictive biomarkers will help decide the treatment of patients with adenocarcinoma?
(4)(2)
- EGFR
- HER2
- KRAS
- BRAF
ALK translocation
ROS1 translocations
Which predictive biomarkers will help decide the treatment of patients with squamous cell carcinoma?
very few
Which type of lug cancer can immunotherapy be used to treat?
NSCLC
The _______ axis immune checkpoint in NSCLC:
- A therapeutic target
- An important biomarker
PD1/PD-L1
