Pathology of Lung Cancer Flashcards
what is the most common cause of death by cancer in Europe?
lung cancer
what percentage of all deaths in Scotland does lung cancer account for?
6%
what are the aetiologies for lung cancer from most important to least?
smoking, asbestos, environment radon, chromates + hydrocarbons + nickel, air pollution and urban environment, other radiation, pulmonary fibrosis
what percentage of lung cancer gets attributed to tobacco?
> 85%
what percentage of smokers get lung cancer?
10%
how does smoking increase the chances of lung cancer?
- epithelial effects
- multi-hit theory of carcinogenesis
- host activation of pro-carcinogens (inherited polymorphisms predispose; metabolism of pro-carcinogens + nicotine addiction)
what are the two pathways of carcinogenesis in the lung?
in the lung periphery and in the central lung airways
what transformations occur in the lung periphery?
bronchioalveolar epithelial stem cells transform
what is the outcome of the lung periphery pathway?
adenocarcinoma
what transformations occur in the central lung airways?
bronchial epithelial stem cells transform
what is the outcome of the central lung airways pathway?
squamous cell carcinoma
which of the two pathways is likely to happen in none-smokers as well as smokers?
the peripheral lung adenocarcinogenesis is less strongly associated with smoking; it does occur in smokers
which oncogene mutation is linked to smoking?
KRAS (35%?)
which oncogenes are not related to tobacco carcinogenesis?
EGFR (15%?), BRAF, HER2 (2% each?), ALK rearrangements (2%?)
what are the different tumours which affect the lung?
- lymphoma
- sarcoma
- metastases (very common)
- benign causes of mass lesion
- carcinoid tumour
- tumours of bronchial glands
what are carcinoid tumours?
- <5% of lung neoplasms
- low grade malignancy
what are tumours of bronchial glands?
either:
- adenoid cystic carcinoma
- mucoepidermoid carcinoma
- benign adenomas
are tumours of bronchial glands common?
NO they are rare
what main types of lung carcinomas are there?
- squamous (40%, stable since 197/80s)
- adenocarcinoma (41%, increase since 197/80s)
- small cell carcinoma (SCLC) (15%, stable since 197/80s)
- large cell carcinoma (4%, decrease since 197/80s)
what is “adenocarcinoma in situ”?
old name given to bronchioloaveolar cell carcinoma, formerly a subtype of adenocarcinoma
which are the non-small cell carcinomas (NSCLC)
adenocarcinoma, squamous cell carcinoma, large cell carcinomas
is NSCLC a single type of lung carcinoma?
NO
why is this term even used then?
sometimes in diagnosis this term is used because no distinction can be made between particular types of non-small cell carcinoma on small biopsy samples
how easily detected is primary lung cancer? why?
- not easily, grow ‘clinically silent” for years
- presents LATE in its natural history
- may have few, in any, signs or symptoms until disease is very advanced
- may be found incidentally, during investigation for something unrelated
- generally speaking, symptomatic lung cancer is fatal
what are the type of local effects of lung cancer?
bronchial obstruction, pleural effects, direct invasion, lymph node metastases
what are the different effects of bronchial obstruction?
- collapse
- endogenous lipoid pneumonia
- infection/ abscess
- bronchiectasis
what are the different pleural effects?
- inflammation
- malignant (tissue destruction?)
where can a local direct invasion happen?
- chest wall
- nerves
- mediastinum (superior vena cava, pericardium)
what happens if the local effect of lung cancer is the direct invasion of nerves?
- if phrenic nerve -> diaphragmatic paralysis
- if L recurrent laryngeal -> hoarse, bovine cough
- if brachial plexus -> pancoast T1 damage
- if cervical sympathetic -> Horner’s syndrome
what are the local effects of lymph nodes metastases?
- mass effect
- lymphangitis carcinomatosa
what is mass effect?
in medicine, a mass effect is the effect of a growing mass that results in secondary pathological effects by pushing on or displacing surrounding tissue
where does lung cancer usually metastase to?
liver, adrenal, bone, brain, skin
what secondary local effects are there?
neural, vascular
does lung cancer also have some non-metastatic distant effects?
yes
non-metastatic paraneoplastic effects of lung cancer: what effects on the skeleton?
- clubbing
- HPOA (hypertrophic pulmonary osteoarthropathy)
non-metastatic paraneoplastic effects of lung cancer: what effects on the endocrine system?
- ACTH, siADH (small cell), PTH (squamous)
- carcinoid syndrome
- gynecomastia
non-metastatic paraneoplastic effects of lung cancer: what neurological effects?
- polyneuropathy
- encephalopathy
- cerebellar degeneration
- myasthenia (Eaton-Lambert)
non-metastatic paraneoplastic effects of lung cancer: what effects on the cutaneous system?
- acanthosis nigricans
- dermatomyositis
non-metastatic paraneoplastic effects of lung cancer: what haematologic effects?
- granulocytosis
- eosinophilia
- DIC
non-metastatic paraneoplastic effects of lung cancer: what effects on the cardiovascular system?
- thrombophlebitis migrans
non-metastatic paraneoplastic effects of lung cancer: what effects on the renal system?
- nephrotic syndrome
how do you investigate lung cancer?
- chest Xray
- bronchoscopy
- trans-thoracic fine needle aspiration
- trans-thoracic core biopsy
- pleural effusion
- advanced imaging techniques
how often is sputum cytology used?
rarely
what are the different types of bronchoscopy?
- bronchial biopsy
- bronchial brushings and washings
- endobronchial US-guided aspiration (EBUS)
what are the different types of imaging techniques used for the investigation of lung cancer?
CT scanning, MRI, PET, other imaging
what factors affect the prognostic of lung cancer?
- stage of disease
- classification (type of disease, according to markers, oncogenes, gene expression profiles, growth rate, cell proliferation, DNA aneuploidy, immune cell infiltration)
why else might prognostic markers be used?
to select patients for adjuvant therapy
how good is the prognosis in lung cancer?
generally dreadful
what are the chances of surviving 5 years in Scotland? the US?
<7% in Scotland, 15% in the US
what if the cancer is operable? is there a correlation with stage?
stage 1 > 60% 5YS
stage 2 35% 5YS
YES
what percentage of lung cancer patients get surgical treatment in Scotland?
around 10%
what is the 5YS % for non-small cell carcinomas?
10-25%
what is the 5YS % for small cell carcinomas?
4%, the median survival is 9 months
which are the predictive markers used to select patients for therapy?
- adenocarcinoma: EGRF, KRAS, HER2, BRAF mutations, ALK translocations etc etc
- squamous cell: FGFR1 gene copy number, DDR2 & FGFR2 mutations etc
