Pathology of Pulmonary Neoplasia Flashcards
Describe lung cancer as a major health issue globally
Very high prevalence and is the number 1 cause of cancer mortality
Lung cancer deaths are expected to increase
What are the some of the causes of lung cancer?
Tobacco
Asbestos
Environmental radon
Air pollution and urban environment
Other occupational exposure, other radiation and pulmonary fibrosis
Explain lung cancer and smoking
More than 85% attributable to tobacco
10% of smokers get lung cancer
Females may be more susceptible
No safe smoking threshold
What does tobacco smoke contribute to in lung cancer?
Epithelial effects
Multi hit theory of carcinogenesis
Host activation of pro-carcinogens - inherited polymorphisms predispose and metabolism of pro-carcinogens
What is the multi-hit theory of carinogenesis?
Number of genomic events have to take place in a specific cell population in the same sequence
Billions of cells so makes it more likely
Describe bronchial epithelial transformation - pathway of lung carcinogenesis?
Bronchial squamous dysplasia
Squamous carcinoma-in-situ
Invasive squamous cell carcinoma
Describe terminal respiratory unit epithelial transformation - pathway of lung carcinogenesis
Atypical adenomatous hyperplasia AAH
Adenocarcinoma-in-situ AIS
Invasive adenocarcinoma
This can also transform into squamous cell carcinoma and become an invasive squamous cell carcinoma
What are some smoking induced oncogenes?
KRAS and EGFR
What are some oncogenes that are not related to tobacco carcinogenesis?
BRF, HER2
ALK
ROS 1
What are the 4 approved targets for oncogenic drivers in adenocarcinomas?
EGFR mutation
ALK rearrangement
ROS1 rearrangement
KRAS G12C mutation
Describe adenocarcinomas and oncogenic drivers
Only a minority are genetically simple with an oncogenic driver
Most are genetically complex
Describe squamous cell carcinomas and targets
Very few suitable targets - very few addictive oncogenes
The commonest alterations are inactivating mutations in tumour suppressor genes
What are thee tumours of the lung?
Benign, Carcinoid tumour, tumours of bronchial glands, lymphoma, sarcoma and metastases (common)
What is a carcinoid tumour?
Type of slow growing cancer in the lung and is a low grade malignancy
What are some tumours of the bronchial glands?
Very rare
Adenoid cystic carcinoma, mucoepidermoid carcinoma and benign adenomas
What are the 4 types of carcinoma of the lung?
Squamous cell
Adenocarcinoma
Small cell carcinoma
Large cell carcinoma
Does tobacco cause more adenocarcinomas or squamous cell carcinoma
Squamous cell carcinoma
What is bronchioloalveolar cell carcinoma now called?
Was a subtype of adenocarcinoma
Now it is called adenocarcinoma in situ
What does in situ mean?
The term carcinoma in situ is a term used to define and describe a cancer that is only present in the cells where it started and has not spread to any nearby tissues
Is the earliest stage of cancer and is termed non-invasive
What are the non-small cell carcinomas (NSCLC)?
Adenocarcinoma
Squamous cell carcinoma
Large cell carcinoma
Others
NSCLC is not a single type of lung carcinoma - sometimes the term is used when we cannot distinguish between
Explain some features of primary lung cancer?
Probably grows clinically silent for many years
Present late in natural history
May only have a few symptoms if disease is very advanced
May be found incidentally
What are some lung cancer local effects which cause bronchial obstruction?
Collapse
Endogenous lipoid pneumonia
Infection/ Abscess - muco-ciliary escalator not working so accumulation of secretion
bronchiectasis
Explain endogenous lipoid pneumonia
Localised accumulation of lipid-laden macrophages within alveoli distal to an obstructed airway
These lipids are difficult to digest and the macrophages, which attempt to phagocytose them, accumulate within the alveolar spaces
What are some pleural local effects of lung cancer?
Inflammatory - effusion
Malignant
What is the sign of phrenic nerve involvement with lung cancer invasion?
Diaphragmatic paralysis
What are the signs of L recurrent laryngeal nerve involvement with lung cancer?
Hoarse and bovine cough due to paralysed voice box
What are the signs of brachial plexus involvement in lung cancer?
Pancoast T1 damage
What are the signs of cervical sympathetic nerve involvement in lung cancer?
Can get Horner’s syndrome - one side of neck and head paralysis
What happens if SVC is invaded by lung cancer?
Caused by malignant tumours in the mediastinum
Face and arm swelling and shortness if breath
Describe lung cancer local effects on lymph nodes?
Can get lymph node metastases
Cause mass effect and can get lymphangitis carcinomastosa
Where can distant metastases be from lung cancer?
Liver, adrenals, bones, brain and skin
What are some skeletal non-metastatic paraneoplastic effects of lung cancer?
Clubbing and HPOA (hypertrophic osteoarthropathy)
What are some endocrine non-metastatic paraneoplastic effects of lung cancer?
Hormone secretion:
ACTH - small cell carcinomas
siADH
PTH - squamous cell carcinomas
Carcinoid syndrome
Gynecomastia
What investigations are used for lung cancer?
Chest X-ray
Bronchoscopy
Trans-thoracic fine needle aspiration
Trans-thoracic core biopsy
Pleural effusion cytology and biopsy
What are some advanced imaging techniques used for lung cancer?
CT scanning
MRI, PET scanning
Other scanning
What are types of bronchoscopy?
Bronchial biopsy
Bronchial brushings and washings
Endobronchial US-guided aspiration (EBUS)
Explain a bronchoscopy
Is a procedure to see inside of airways and remove a small sample of cells
A thin tube with a camera at the end, called a bronchoscope, is passed through your mouth or nose, down your throat and into your airways
Explain an EBUS?
Combines a bronchoscopy with an ultrasound scan.
An EBUS allows to see the inside of your airways. However, the ultrasound probe on the end of the camera also allows the doctor to locate the lymph nodes in the centre of the chest so they can take a biopsy from them
What are prognostic factors in Lung cancer?
Stage of disease
Classification - type
Markers/ oncogenes/ gene expression profiles
Might be used to select patients for adjuvant therapy
What is the prognosis in lung cancer?
Generally nor good
There is overall correlation with stage
In Scotland, around 12-15% of patients with lung cancer get surgical treatment
Explain predictive factors in lung cancer?
After diagnosis is made predictive biomarkers will increasingly be used to select patients for therapy
What are predictive biomarkers for adenocarcinomas and squamous cell carcinomas?
Adenocarcinomas - EGRF, KRAS mutations, ALK and R0S1 translocations etc.
Squamous cell - little or no effective molecular targeted therapies
What biomarker can be used in NSCLC?
The PD1/ PD-L1 axis immune checkpoint
This is a therapeutic target
Explain therapeutic against cancer hallmarks
PD1, PD-L1 and CTLA4 are immune checkpoints adopted by tumours to avoid immune destruction
Drugs against these checkpoints are gaining increased use in lung and other cancer therapies
