Respiratory pathology Flashcards by Monira K

What are common symptoms of lung cancer?

Haemoptysis (coughing up blood)
Cough 
Chest/Shoulder Pain
Dyspnoea
Recurrent infections

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what is TNM staging?

Tumour
Nodes
Metastases

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what is the T stage dependant on?

T staging is based on:

Location
Size
Proximity to other organs

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what can cause higher T staging?

If the tumour is closer to the mediastinum or the chest wall then it has a HIGHER T STAGING.
-this is irrespective of its size.

if the tumour spreads to the lymph nodes in the neck then there is higher staging

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when is surgery not practical?

If the lymph nodes has spread to the lymph nodes

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How do PET scans work?

Patients fast for 4 hours and are then given radiolabelled glucose
the lungs are not metabolically active but the tumour is very metabolically active
the kidneys are naturally very metabolically active

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what are the features for Small cell lung cancer?

Usually grows rapidly and metastasise early

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what is the treatment for small cell lung cancer?

Chemotherapy and radiotherapy

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What is the best treatment for local non-small cell lung cancer, if it is localised?

Surgery

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what is measurement when we can make a diagnosis of the tumour?

10 mm.

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How can samples be acquired for cytological analysis?

Cytology - looking at individual cells

Sputum
Bronchial washings and brushing
Pleural fluid
Endoscopic fine needle aspiration of tumour/enlarged lymph nodes
lavage

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How can samples be acquired for histological analysis?

Histology - looking at tissues

Biopsy

Central tumour - bronchoscopy
Peripheral tumours - CT guided biopsy through skin

Surgical biopsy :

Mediastinal lymph node biopsy - for staging
Open biopsy at time of surgery if lesion not accessible otherwise - “frozen section”
Ultimate “biopsy” Resection specimen - confirm excision and staging

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what type of cells can tumours form from?

epithelial
mesenchymal (soft tissue)
Lymphoid

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what are some features of benign tumours?

Do not metastasise
can cause local complications e.g. obstruction of the airways
Do NOT invade adjacent tissues
grow more slowly

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What are the three types of non-small cell carcinoma? What percentage of lung cancers are non-small cell?

Non-Small Cell = 80%

Squamous cell carcinoma
Adenocarcinoma
Large cell carcinoma

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How are the incidences of squamous cell carcinoma and adenocarcinoma changing?

Squamous cell carcinoma incidence is decreasing

Adenocarcinoma incidence is increasing- this is the most common form of lung cancer among Non-smokers.

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Where do squamous cell carcinomas and adenocarcinomas tend to arise?

Squamous cell carcinoma (metastasise late)

tends to arise near the mediastinum
in the airways (traditionally central arising - from bronchial epithelium)

Adenocarcinoma (metastasise early)
- tends to arise near the periphery

*recently has been increase in peripheral squamous cell carcinoma - people are inhaling the smoke more deeply

State three major risk factors for lung cancer.

Smoking, Radiation, Asbestos Exposure

What are the four stages in the pathway to carcinoma?

Normal epithelium
Hyperpalsia
Squamous Metaplasia
Dysplasia
Carcinoma in situ
Invasive Carcinoma

Multistep accumulation of mutations resulting in:

Disordered growth, loss of cell adhesion, invasion of tissue by tumour, stimulation of new vessel formation around tumours
Mutations occur in epithelial cells and stem cells.
Pathways different for different tumour types

Why has a precursor lesion for small cell lung carcinoma not been found?

Because small cell carcinoma grows too quickly and it metastasises early

How do the cells lining the airways change in squamous cell carcinoma?

The ciliated cells undergo metaplasia due to the chronic stimulation by cigarette smoke to become squamous cells
As there is no cilia on the epithelium any more, the mucus will stay in your lungs so you get smoker’s cough
The squamous cells begin to acquire mutations which means that its normal pattern of growth is disrupted
The dysplasia becomes more and more disordered so it becomes carcinoma in situ
A further mutation will make it invasive so that it can invade neighbouring tissue and lymphatics

Which type of lung cancer is common in non-smokers?

Adenocarcinoma

Which types of lung cancer are strongly associated with smoking?

Small cell carcinoma

Squamous cell carcinoma

Describe the cytological features of squamous cell carcinoma.

Large Nuclei

Keratin in cytoplasm

What is the precursor lesion for adenocarcinoma and where does it form from?

Forms from glandular epithelium Atypical Adenomatous Hyperplasia- proliferation of atypical cells lining the alveolar walls. increases in size and can eventually become invasive

At what point does adenocarcinoma in situ become invasive adenocarcinoma?

When the cells develop a mutation so that they can break down the stroma and become invasive. The breaking down of the stroma causes inflammation and leads to the formation of fibrous tissue. The invasive tumour can break down the elastin in the basement membrane and form the pink fibrous stroma.

Describe the cytological features of adenocarcinoma.

Adenocarcinoma shows glandular differentiation. They have big atypical nuclei with mucin globules. -the blue around the outside: you can see BIG atypical nuclei and the rest of the cytoplasm is filled with mucin globule

Where does adenocarcinoma usually develop and are they usually multi-focal?

Adenocarcinoma normally develops near the periphery and they ARE usually multi-focal in the lungs and tend to spread early.

What are the two molecular pathways for adenocarcinoma and which one is associated with smoking?

K ras - associated with smoking (DNA methylation + p53) | EGFR - responder or resistance mutations. Epidermal growth Factor Receptor

Why is it important to differentiate between the different pathways?

K ras mutation means that it is unlikely to respond to targeted therapies EGFR responder mutation, need to identify whether it is responder mutation or a resistance mutation, as this could mean that the patient has an almost complete regression even in very advanced disease.

What is large cell carcinoma?

POORLY differentiated carcinoma - has a poor prognosis Electron microscopy shows some evidence of squamous/neuroendocrine differentiation suggesting that they could be very poorly differentiated squamous cell carcinoma or adenocarcinoma

What are the cytological features of small cell carcinoma?

WORST form of lung cancer. | They look like lymphocytes. Large nucleus and little cytoplasm. Basically just nuclei with a small amount of cytoplasm

Where does small cell carcinoma tend to arise?

Often arise central near the bronchi. - very common in smokers - divide so fast, the tumour often outgrows its blood supply and becomes necrotic.

What does the ERCC1 (Excision Repair Cross-complementation Group 1 protein) marker determine?

ERCC1 positive means that advanced non-small cell lung cancer is unlikely to respond to cisplatin.

What type of receptor is EGFR and what is used to block this receptor?

-EGFR sits on the surface of cells and signals a variety of downstream pathways that make the cell divide It is a Tyrosine kinase receptor, this regulates angiogenesis, proliferation, apoptosis and migration - tyrosine kinase inhibitors work against this

What are paraneoplastic syndromes?

Systemic effect of tumour due to systemic effect of tumour due to abnormal expression by tumour cells of factors (e.g. hormones) NOT normally expressed by the tissue from which the tumour arose

State some endocrine paraneoplastic syndromes.

SIADH (inappropriate ADH): small cell carcinoma Cushing's Syndrome (producing ectopic ACTH): small cell carcinoma Parathyroid hormone-related peptides----hypercalcaemia: squamous cell carcinoma

What is strongly associated with mesothelioma?

Asbestos

What is the TNM system used for?

It is used to determine prognosis and operability

how does the mesothelioma infect?

- there is a LONG LAG TIME: tumour develops decades after exposure. more common in males