Pathology of Pulmonary Neoplasia

Question 1

Describe lung cancer as a major health issue globally

Answer 1

Very high prevalence and is the number 1 cause of cancer mortality
Lung cancer deaths are expected to increase

Question 2

What are the some of the causes of lung cancer?

Answer 2

Tobacco
Asbestos
Environmental radon
Air pollution and urban environment
Other occupational exposure, other radiation and pulmonary fibrosis

Question 3

Explain lung cancer and smoking

Answer 3

More than 85% attributable to tobacco
10% of smokers get lung cancer
Females may be more susceptible
No safe smoking threshold

Question 4

What does tobacco smoke contribute to in lung cancer?

Answer 4

Epithelial effects
Multi hit theory of carcinogenesis
Host activation of pro-carcinogens - inherited polymorphisms predispose and metabolism of pro-carcinogens

Question 5

What is the multi-hit theory of carinogenesis?

Answer 5

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

Question 6

Describe bronchial epithelial transformation - pathway of lung carcinogenesis?

Answer 6

Bronchial squamous dysplasia
Squamous carcinoma-in-situ
Invasive squamous cell carcinoma

Question 7

Describe terminal respiratory unit epithelial transformation - pathway of lung carcinogenesis

Answer 7

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

Question 8

What are some smoking induced oncogenes?

Answer 8

KRAS and EGFR

Question 9

What are some oncogenes that are not related to tobacco carcinogenesis?

Answer 9

BRF, HER2
ALK
ROS 1

Question 10

What are the 4 approved targets for oncogenic drivers in adenocarcinomas?

Answer 10

EGFR mutation
ALK rearrangement
ROS1 rearrangement
KRAS G12C mutation

Question 11

Describe adenocarcinomas and oncogenic drivers

Answer 11

Only a minority are genetically simple with an oncogenic driver
Most are genetically complex

Question 12

Describe squamous cell carcinomas and targets

Answer 12

Very few suitable targets - very few addictive oncogenes
The commonest alterations are inactivating mutations in tumour suppressor genes

Question 13

What are thee tumours of the lung?

Answer 13

Benign, Carcinoid tumour, tumours of bronchial glands, lymphoma, sarcoma and metastases (common)

Question 14

What is a carcinoid tumour?

Answer 14

Type of slow growing cancer in the lung and is a low grade malignancy

Question 15

What are some tumours of the bronchial glands?

Answer 15

Very rare
Adenoid cystic carcinoma, mucoepidermoid carcinoma and benign adenomas

Question 16

What are the 4 types of carcinoma of the lung?

Answer 16

Squamous cell
Adenocarcinoma
Small cell carcinoma
Large cell carcinoma

Question 17

Does tobacco cause more adenocarcinomas or squamous cell carcinoma

Answer 17

Squamous cell carcinoma

Question 18

What is bronchioloalveolar cell carcinoma now called?

Answer 18

Was a subtype of adenocarcinoma
Now it is called adenocarcinoma in situ

Question 19

What does in situ mean?

Answer 19

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

Question 20

What are the non-small cell carcinomas (NSCLC)?

Answer 20

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

Question 21

Explain some features of primary lung cancer?

Answer 21

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

Question 22

What are some lung cancer local effects which cause bronchial obstruction?

Answer 22

Collapse
Endogenous lipoid pneumonia
Infection/ Abscess - muco-ciliary escalator not working so accumulation of secretion
bronchiectasis

Question 23

Explain endogenous lipoid pneumonia

Answer 23

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

Question 24

What are some pleural local effects of lung cancer?

Answer 24

Inflammatory - effusion
Malignant

Question 25

What is the sign of phrenic nerve involvement with lung cancer invasion?

Answer 25

Diaphragmatic paralysis

Question 26

What are the signs of L recurrent laryngeal nerve involvement with lung cancer?

Answer 26

Hoarse and bovine cough due to paralysed voice box

Question 27

What are the signs of brachial plexus involvement in lung cancer?

Answer 27

Pancoast T1 damage

Question 28

What are the signs of cervical sympathetic nerve involvement in lung cancer?

Answer 28

Can get Horner's syndrome - one side of neck and head paralysis

Question 29

What happens if SVC is invaded by lung cancer?

Answer 29

Caused by malignant tumours in the mediastinum Face and arm swelling and shortness if breath

Question 30

Describe lung cancer local effects on lymph nodes?

Answer 30

Can get lymph node metastases Cause mass effect and can get lymphangitis carcinomastosa

Question 31

Where can distant metastases be from lung cancer?

Answer 31

Liver, adrenals, bones, brain and skin

Question 32

What are some skeletal non-metastatic paraneoplastic effects of lung cancer?

Answer 32

Clubbing and HPOA (hypertrophic osteoarthropathy)

Question 33

What are some endocrine non-metastatic paraneoplastic effects of lung cancer?

Answer 33

Hormone secretion: ACTH - small cell carcinomas siADH PTH - squamous cell carcinomas Carcinoid syndrome Gynecomastia

Question 34

What investigations are used for lung cancer?

Answer 34

Chest X-ray Bronchoscopy Trans-thoracic fine needle aspiration Trans-thoracic core biopsy Pleural effusion cytology and biopsy

Question 35

What are some advanced imaging techniques used for lung cancer?

Answer 35

CT scanning MRI, PET scanning Other scanning

Question 36

What are types of bronchoscopy?

Answer 36

Bronchial biopsy Bronchial brushings and washings Endobronchial US-guided aspiration (EBUS)

Question 37

Explain a bronchoscopy

Answer 37

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

Question 38

Explain an EBUS?

Answer 38

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

Question 39

What are prognostic factors in Lung cancer?

Answer 39

Stage of disease Classification - type Markers/ oncogenes/ gene expression profiles Might be used to select patients for adjuvant therapy

Question 40

What is the prognosis in lung cancer?

Answer 40

Generally nor good There is overall correlation with stage In Scotland, around 12-15% of patients with lung cancer get surgical treatment

Question 41

Explain predictive factors in lung cancer?

Answer 41

After diagnosis is made predictive biomarkers will increasingly be used to select patients for therapy

Question 42

What are predictive biomarkers for adenocarcinomas and squamous cell carcinomas?

Answer 42

Adenocarcinomas - EGRF, KRAS mutations, ALK and R0S1 translocations etc. Squamous cell - little or no effective molecular targeted therapies

Question 43

What biomarker can be used in NSCLC?

Answer 43

The PD1/ PD-L1 axis immune checkpoint This is a therapeutic target

Question 44

Explain therapeutic against cancer hallmarks

Answer 44

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