Flashcards in 15. Pathology of Lung Cancer ( pulmonary neoplasia) Deck (91):
Does lung cancer kill more than breast and prostate cancers combined?
Yes; it's the most common cause of cancer related deaths worldwide
What place is lung caner in terms of mortality?
1st for mortality accounting for 353,000 deaths (3rd for highest incidence of all cancer)
Name the 4 top cancers in Europe with highest incidences. (in 2012)
1. female breast cancer
2. colorectal cancer
3. prostate cancer
4. lung cancer
What percentage of deaths in Scotland does lung cancer approximate for?
6% of all deaths in Scotland (in males on the rise)
What are the 7 main aetiological factors (causes) for lung cancer from top cause to bottom?
3. environmental radon (accumulation in granite-type rocks)
4. other occupational exposure ( chromates, hydrocarbons, nickel)
5. air pollution and urban environment
6. other radiation
7. pulmonary fibrosis
What is the current trend for males and females in terms of smoking?
- for males smoking is decreasing
-for females smoking is increasing
What percentage of lung cancer patients are smokers?
>85% (due to tobacco)
What percentage of smokers get lung cancer?
10% (but majority of other get other resp. failure disease and conditions)
By smoking, how much is the risk of getting cancer increased by for females and males?
- For females, the risk is increased 22 times
-For males, the risk is increased 12 times
Are males or females more susceptible to tobacco smoke?
What is lung cancer risk directly related to?
Consumption; inhalation and pack years (packs per day per year)
What percentage of lung cancers are so-colled "non-smoking cancers"?
at least 25%
Through passive smoking, what is the increased percentage risk of getting cancer?
Does risk of getting lung cancer reduces with smoking abstinence?
Yes but very slowly (over 50% lung cancers are ex-smokers)
What fraction of UK population smokes?
1/3 (worldwide 50% men and 12% women)
How many carcinogens are there roughly in a whiff of smoke?
How many chemical compounds are found in a whiff of smoke?
Which type of cancer are n-carcinogens more responsible for?
Describe the multi-hit theory of carcinogenesis.
- Approx. 3-12 key molecular changes in a specific sequence need to occur in a stem cell population to get clinical lung cancer (invasive phenotype). Depending on our genetics +detoxifying mechanisms, we deal with these differently.
- host activation of pro-carcinogens are due to inherited polymorphisms which predispose.
- metabolism for carcinogens and nicotine addiction influenced causing epithelial effects
What are 2 main pathways of carcinogenesis in the lung? (2 main areas where cancer development occurs)
1. in lung periphery
2. in the central lung airways
What transformations occur in the lung periphery? What cancer do they lead to?
- Bronchioalveolar epithelial stem cells transform
What transformations occur in the central lung airways? What cancer do they lead to?
-bronchial epithelial stem cells transform
- more sensitive to polycyclic squamous cell carcinoma
What is squamous dysplasia forming carcinoma in-situ strongly associated with?
Does peripheral lung adenocarcinogenesis associated with smoking?
Less strongly, it also does occur in non- smokers (more than squamous dysplasia)
Describe the 3 stages of formation of an ademocarcinoma.
1. atypical adenomatous hyperplasia (AAH)
2. adenocarcinoma in situ
3. invasive adenocarcinoma
What gene mutation is the most common in adenocarcinma patients and is therefore smoking induced?
Adenocarcinoma makes up what percentage of all lung cancers?
Which 4 gene mutations are NOT related to tobacco carcinogenesis?
4. ALK rearrangements
What mechanism is the key driver for mutations?
oncogene addiction (by cells)
Is lung a common place for metastases?
What are the various types of "tumours" in the lung? (6)
1. benign causes of mass lesion
2. carcinoid tumour
3. tumours of bronchial glands (V. RARE)
6. Metastases to lungs from other body regions
What is a carcinoid tumour?
- rare cancer of neuroendocrine system affecting hormone production
- tends to grow very slowly
- can affect; bowels, appendix, stomach, pancreas, kidneys, breast, ovaries, testes and lungs
- low grade malignancy
Carcinoid tumours make up what percentage of lung neoplasms?
What are 3 types of tumour of bronchial glands?
1. adenoic cystic carcinoma
2. mucoepidermoid carcinoma
3. benign adenomas
What are the 4 main types of carcinomas of the lung? (from most to least prevalent)
1. squamous cell
3. small cell carcinoma
4. large cell carcinoma
What is the bronchioloalveolar cell carinoma (alveolar cell carcinoma) now walled?
adenocarcinoma in situ (subtype of adenocarcinoma)
Do small or non-small carcinomas make up 85% of all lung carcinomas?
Non-small cell carcinomas (NSCLC)
What percentage of all lung cancers do small cell carcinomas (SCLC) make up?
What are the main non-small cell carcinomas? (4)
2. squamous cell carcinoma
3. large cell carcinoma
Are non-small cell carcinomas a single type of lung carcinoma?
- NO; NSCLC are not unified disease, it's a GROUP of very biologically different and diverse diseases which have to be treated in different ways.
- this term is used when non-small cell carcinomas cannot be distinguished on small biopsy samples
How it can be identified if a person has a small or non-small cell carcinoma?
Using a microscope and looking at biopsy slides
Does primary lung cancer present itself clinically early or late in its natural history?
- grows clinically silent for many years in early stages
- presents LATE
-may have very little if any signs or symptoms until disease is advanced and progressed
When is primary lung cancer often found in patients?
Sometimes incidentally during an investigation for something unrelated
What does symptomatic lung cancer tell us about the disease?
most likely fatal and incurable
When can surgeons resect the disease?
Only when it's in early stages and no spread outside the thorax (no mets)
What are 4 local effects of lung cancer?
1. bronchial obstruction
3. direct invasion
4. lymph node metastases
What are 4 main effects of lung cancer specifically leading to bronchial obstruction?
2. endogenous lipoid pneumonia
3. infection/ abscess
(mucous escalator in airways is blocked )
What can yellow spots on a lung suggest?
1. bronchial cartilages meaning lobe is collapsed (because of bronchiole obstruction)
2. fat filled macrophages which accumulate in airways and obstruct
What are the local effects of lung cancer on pleural regions? (2)
In local effects of lung cancer, where does the direct invasion occur?
invasion into the chest wall (it doesn't necessarily rule out surgery)
Lung cancer local effects can often lead to direct invasion into which nerves specifically? (4)
1. phrenic nerves
2. L recurrent laryngeal (branch of vagus nerve)
3. brachial plexus
4. cervical sympathetic
What can local invasion into phrenic nerves lead to?
What can local invasion into L recurrent laryngeal nerve lead to?
hoarse, bovine cough ( dry/ harsh cough)
What can local invasion into brachial plexus lead to?
pancoast T1 damage
What can local invasion into cervical sympathetic nerves lead to?
Into which two regions in the mediastinum can direct invasion of lung cancer spread to?
- superior vena cava (SVC)
What symptom can invasion into superior vena cava cause?
excessive oedema and swelling (due to impaired circulation)
What 2 local effects does direct invasion from lung cancer have on lymph node mets?
1. mass effect
2. lymphangitis carcinomatose (inflammation of lymph vessels)
Lymph nodes found where are most commonly involved in metastasis of lung cancer? (2)
Lymph nodes found in
(spreads into hilum the mediastinal lymph nodes)
Where do DISTANT metastases occur in lungs? (5)
What are distant effects of lung cancer which are secondary to local effects?
What are 3 forms of distant effects of lung cancer in the body?
1. distant metastases
2. secondary to local effects
3. non-metastatic effects (caused by hormonal changes in the body)
Why do non-metastaitic effects of lung cancer cause so many changes in the body?
They are mediated by auto-imune system which tricks the tumour to damage its own cells
What are the non-metastatic paraneoplastic effects of lung cancer on skeletal system? (2)
2. HPOA;hypertrophic osteoarthropathy (proliferation of skin and tissues, side effect of lung cancer)
What are the non-metastatic paraneoplastic effects of lung cancer on endocrine system? (3)
1. ACTH, ADH, PTH (adenocorticotrophic hormone, antidiruetic hormone, parathyroid hormone)
2. carcinoid syndrome (mets in liver usually release seratonin causing a collection of symptoms)
What are the non-metastatic paraneoplastic effects of lung cancer on neurological system? (4)
2. encephalopathy (general term for disease affecting structure and function of brain)
3. cerebellar degeneration
4. myasthenia (Eaton-Lambert; muscle weakness)
What are the non-metastatic paraneoplastic effects of lung cancer on cutaneous system? (2)
1. acanthosis nigricans (hyperpigmentation of skin)
2.dermatomyositis (inflammation, causes rash)
What are the non-metastatic paraneoplastic effects of lung cancer on haematologic system? (3)
1. granulocytosis (increase in granulocutes whihc are neutrophils)
3. DIC; disseminated intravascular coagulation (overreactive coagulation)
What are the non-metastatic paraneoplastic effects of lung cancer on renal system? (1)
1. nephrotic syndrome (proteins are leaked into urine from kidneys)
Small cell carcinomas are what type what types of tumours?
neuroendocrine tumours (they secrete hormones; ADH and ACTH etc and other molecules)
A person with abnormal ADH levels due to a neuroendocrine tumour can appear to have what condition? (common clinical misdiagnosis)
Squamous carcinomas lead to abnormal levels of which hormone?
PTH; parathyroid hormone
What are 7 main investigation done for lung cancers?
1. chest x ray
2. sputum cytology (rarely used)
4. trans-thoracic fine needle aspiration
5. trans-thoracic core biopsy
6. pleural effusion
7. advanced techniques (CT, MRI, PET, other imaging)
What are 3 forms of bronchoscopy?
1. bronchial biopsy
2. bronchial brushings and washings
3. endobronchial ultrasound guided aspiration (EBUS)
What is the main disadvantage of less invasive procedures used for investigation of lung cancer?
Smaller samples are sent to labs for diagnosis; this means it's harder to fully diagnose and establish cancer type and staging
What are 2 main prognostic factors which need to be identified in lung cancer?
1. STAGE of disease
2. CLASSIFICATION (type of disease)
What is adjuvant therapy?
- "additional therapy"
- chemotherapy, hormone therapy or radiotherapy follows surgery to improve the patient's prognosis/ outcome
- decreases the risk of cancer recurring following surgery
(neoadjuvant is the therapy step BEFORE the main treatment e.g. surgery)
What is used to select patients for adjuvant therapy or any forms of treatment?
Prognostic predictive biomarkers
What is the usual prognosis for lung cancer?
-Generally dreadful; <7%
- survive 5 year survival rate
- overall correlation with stage
What is prognosis in % for Stage 1 lung cancer (operable)?
>60% 5YS (5 year survival)
What is prognosis in % for Stage 2 lung cancer (operable)?
35% 5YS (5 year survival)
In Scotland, what percentage of patients with lung cancer receive surgical treatment?
What stages are "operable" lung cancers?
stages 1 and 2
What is the survival rate range for non-small cell carcinomas?
What is the survival rate range for small cell carcinomas?
- 4% (median survival is 9 months)
- very little can be done
What main mutations occur in adenocarciomas? (non-small) (5)
5. ALK translocations etc
What main mutations occur in squamous cell carcinomas? (non small) (3)
1. FGFR1 gene copy number
3. FGFR2 mutations etc
What 2 mutations only have drugs to treat them?
2. ALK translocations
What are immune checkpoints?
- control immune reactions
- adopted by tumours to avoid immune destruction
What 3 mutations are involved in immune checkpoints in tumours and have drugs developed against them (immune checkpoint inhibitors) which are becoming more popular in lung cancer therapy?
(they switch our immune system off and make tumour evade it)