Lung Cancer Flashcards
What are the types of lung cancer?
- Small cell lung cancer
- Non-small cell lung cancer e.g. SCC or adeno
- Other: Mesothelioma, Pancoast tumours, Secondary lung cancer.
Which lung cancer is more common?
NSCLC (80% of all lung cancers)
SCLC (20%) →smokers, central, Lambert Eaton myasthenic syndrome
Name a benign tumour of the lung.
Chondroma
What are the types of non small cell lung cancer?
Adenocarcinoma(30%) - most common.
Squamous cell carcinoma (30%)
Large cell carcinoma (20%)
Undifferentiated non small cell lung carcinoma - e.g. sarcomatoid carcinoma
Where are adenocarcinomas usually located in the lung? Where are squamous cell carcinomas located?
Adenocarcinomas - located peripherally in the lungs but early metastases
Squamous cell carcinomas - central airways (metastasise later in the disease course), late metastases PTHrP
What are the risk factors for developing lung cancer?
- Tobacco (passive too)- aromatic hydrocarbons, aromatic amines, N-nitrosamines, organic and inorganic compounds.
- Family history
- COPD
- Radon gas - radioactive decay product of uranium which can decay into progeny that emit alpha particles which damage DNA
- Old age
- Asbestos(weak for NSCLC)
What are the most common symptoms associated with lung cancer?
- Cough
- Dyspnoea
- Haemoptysis
- Chest /shoulder pain
- Weight loss
- But may present with symptoms of metastases the most common of which is brain → confusion, personality change, seizures, weakness, focal neurological deficits, nausea and vomiting, and headaches.
What signs are associated with lung cancer?
- Cachexia (weakness+wasting due to chronic illness)
- Anaemia
- Clubbing
- Hypertrophic pulmonary osteoarthropathy - painful arthropathy with periosteal new bone formation. More common in adenocarcinoma.
- Supraclavicular or axillary nodes
Chest signs: none or consolidation/collapse/pleural effusion
Metastases: bone tenderness, hepatomegaly, confusion, fits, local CNS signs, cerebellar syndrome, proximal myopathy, peripheral neuropathy
What complications are associated with lung cancer?
Local:
- recurrent laryngeal nerve palsy
- phrenic nerve palsy
- SVC obstruction
- Horner’s syndrome(Pancoast tumour)
- rib erosion
- pericarditis
- AF
Metastatic:
- brain
- bone (bone pain, anaemia, increased Ca)
- liver
- adrenals (Addison’s)
Non-metastatic:
- confusion
- fits
- cerebellar syndrome
- proximal myopathy
- neuropathy
- polymyositis
- Lambert-Eaton syndrome
Other:
- Horner’s syndrome
- Facial swelling
- Dilated neck or abdominal wall veins
Why is there sometimes shoulder pain in lung cancer?
Lungs have no pain nerve fibres but sometimes tumours invade the pleura or chest wall which can cause chest discomfort early on.
What is the cause of hoarseness in lung cancer?
Recurrent laryngeal nerve paralysis
What is the cause of
- Horner’s syndrome
- Facial swelling
in lung cancer?
Horner’s syndrome (triad of ptosis, miosis and ipsilateral anhydrosis) - in patients with superior sulcus tumours which can invade the sympathetic plexus.
Facial swelling - compression of the vena cava due to mediastinal adenopathy or right upper lobe tumour extending into the mediastinum. Chest/abdominal veins may also be distended due to compression of the vena cava.
Which type of lung cancer is clubbing more common in?
More common in NSCLC than in small cell lung carcinoma.
What is the origin of these cancers?
Adenocarcinoma
Squamous cell carcinoma
Adenocarcinoma - tumour of the glandular epithelial cells (Pappiloma = epithelial)
Squamous cell carcinoma - squamous cells (found in respiratory and digestive tracts, skin, vagina, cervix)
Which type of lung cancer is associated with hypercalcaemia?
Any that cause paraneoplastic syndromes
Squamous cell carcinoma - secretes PTH like compound –> hypercalcaemia .
But paraneoplastic syndrome is more commonly associated with small-cell lung cancer.
What is the most common type of lung cancer in a patient who hasn’t smoked?
ADENOCARCINOMA (the bronchioalveolar subtype being more common in females who have never smoked)
What is the hypertrophic osteoarthritis triad?
Clubbing, long bone swelling, arthritis
What is the patttern of growth in an adenocarcinoma?
Lepidic growth pattern - replaces type I pneumocytes ( but no invasion of interstitium)
Can be multifocal and bilateral
Which paraneoplastic syndromes are associated with small cell carcinoma?
- ACTH –> Cushing’s. ACTH can cause bilateral adrenal hyperplasia and high levels of cortisol can also lead to hypokalaemic alkalosis.
- ADH –> hyponatraemia
- Lambert-Eaton myasthenic syndrome (LEMS) - immune system antibodies attack calcium channels causing myasthenic like syndrome
Where in the lung do SCLC arise?
Centrally or periperally
What are the pros and cons of a small-cell carcinoma?
Cons:
- Fast-growing
- Rapidly progression and early metastases
- Often high stage (spread. NB: grade=differentation)
BUT
- Highly responsive to chemo/rad treatment
- Exclusively in smokers
Where are large cell lung carcinomas typically found? What can they secrete? What is the prognosis?
- typically peripheral
- anaplastic, poorly differentiated tumours with a poor prognosis
- may secrete β-hCG
What are the features of small-cell lung cancer?
- Usually central
- Arise from APUD cells
- Associated with ectopic ADH(vasopressin), ACTH
Which type of lung cancer would you rather have and why?
Non small cell because small-cell is usually (in 2/3) metastatic by the time of diagnosis
What are APUD cells?
An acronym for
- Amine - high amine content
- Precursor Uptake - high uptake of amine precursors
- Decarboxylase - high content of the enzyme decarboxylase
These are the cells that small cell lung cancers usually arise from.
What is the origin of a mesothelioma? Which lung is most often affected? Where does it metastasise to?
Malignancy of the mesothelial cells of the pleura
Metastases to contralateral lung and peritoneum
Right lung affected more than left
How does a mesothelioma present?
- Dyspnoea, weight loss, chest wall pain
- Clubbing
- Painless pleural effusion (30%)
- History of asbestos exposure (in 85-90% with latency of 20-40 years)
- It is rare but has a poor prognosis
What are the risk factors for mesothelioma?
- Asbestos exposure
- Radiotherapy
- Genetic predisposition e.g. BAP1 gene and simian virus 40 (SV-40), also BRCA1
How does asbestos exposure lead to cancer?
Asbestos fibres lead to recruitement and activation of macrophages, neutrophils → generation of iron-catalysed reactive oxygen and nitrogen species
Chronic inflammation + oxidative stress -→ DNA damage –> alterations in gene expression –> malignancy
Variants:
- Pleural (90%)
- Peritoneal (5-10%)
- Pericardial (<1%)
- Testicular<1%)
Which cells do small cell carcinomas arise from?
Kulchitsky cells (endocrine cells) and they often release polypeptide hormones resulting in paraneoplastic syndromes.
What tests would you do if you suspect lung cancer?
- CX - peripheral nodule, hilar enlargement, consolidation, lung collapse, pleural effusion, bony secondaries
- Cytology - sputum and pleural fluid ( at least 20mL)
- Fine needle aspiration/biopsy - peripheral lesions, lymph nodes
- CT to stage the tumour and guide bronchoscopy
- Bronchoscopy - to give histology and assess operability +/- endobronchial US for assessment and biopsy
- 18F-deoxyglucose PET or PET/CT EBUS scan to help staging
- Radionucleotide bone scan - for metastases
- Lung function tests - help assess suitability for lobectomy
What are some non-metastatic extrapulmonary manifestations of bronchial cancer?
Endocrine - Cushings (ACTH), ADH(dilutional hyponatraemia), PTH (hypercalcaemia), HCG (gynaecomastia)
Neurological - cerebellar degeneration, myopathy, myasthenic syndrome
Vascular- thrombophlebitis migrans, anaemia, DIC
Cutaneous - dermatomyositis, herpes zoster, acanthosis nigricans
Skeletal - clubbing, HPOA (hypertrophic osteoarthropathy)
Which NSCLC is more common in non-smokers?
Adenocarcinoma which is more likely periphral than central - might see glands or mucin production
What % of lung cancer in smokers is due to passive smoking?
25%
What are the steps leading to development of carcinoma?
- Metaplasia –> Dysplasia –> Carcinoma in situ –> Invasive carcinoma
- Due to an accumulation of gene mutations
What are the histological features of adenocarcinoma of the lung?
- Gland formation
- Papillae formation
- Mucin
- Histology shows evidence of glandular differentiation
- Kras an P53 common, EGFR in non smokers
Why is small cell lung cancer prognosis poor?
Often poorly differentiated and grow quickly so outgrow their blood supply and develop a necrotic core
P53 and RB1 mutation
2-4 month survival untreated, 10-20 months on treatment usually by chemotherapy
Why is it important to distinguish between type of NSCLC i.e. adeno or SCC, for treatment purposes?
If SCC is treated with biologics used for adenocarcinoma e.g. bebevacizumab, it can cause fatal haemorrhage
Adenocarcinoma targets:
- EGFR mutation (responder or resistance) - TKi
- ALK translocation (responds to Crizotinib)
- Ros1 translocation
- PD-L1 expression
SCC targets:
- PDL1 expression (expression inhibits immune response)
What investigations would you do for lung cancer?
2WW referral
CXR then CT contrast - neck, thorax, upper abdomen
Bronchoalveolar lavage:
-
Cytology – looking at cells:
- Sputum
- Bronchial washings and brushings
- Pleural fluid or effusion fluid
- Endoscopic fine needle aspiration of tumour/enlarged lymph nodes
-
Histology – looking at tissue:
- Biopsy at bronchoscopy – central tumours
- Percutaneous CT guided biopsy – peripheral tumours
- Mediastinoscopy and lymph node biopsy – for staging
- Open biopsy at time of surgery if lesion not accessible otherwise - frozen section
- Resection specimen - confirm excision and staging
Staging: PET-CT to assess for metastases; VATS; bone scan; CT head
Bloods: FBC, clotting, LFTs, chemistry panel, ALP
What are the endocrine/non-endocrine features of paraneoplastic syndrome?
Endocrine:
- (1) ADH –> hyponatremia (SCC)
- (2) ACTH –> Cushing’s syndrome (SCC)
- (3) PTH –> hypercalcaemia (SCC)
- (4) Other:
- Calcitonin –> hypocalcaemia
- Gonadotropins –> gynecomastia
- Serotonin –> “carcinoid syndrome” (especially carcinoid tumours; rarely SCC)
Non-endocrine:
- Haematological/coagulation defects, skin, muscular, miscellaneous
What is the management of lung cancer?
Stage I to IIIA are potentially curable
- MDT management
- Surgical resection e.g. lobectomy or pneumonectomy is preferred over wedge resection
- +/- Adjuvant chemo/radiotherapy - e.g. atezolizumab (PD1), platinum based chemotherapy
Other
- Stereotactic radiosurgery or radiotherapy - for brain metastases
- Palliative radiotherapy - relieves symptoms like haemoptysis, chest pain, SOB
What are the complications of treatment with lung cancer?
Intraoperative and postoperative:
- haemorrhage,
- infection,
- cardiac ischaemia,
- stroke,
- cardiac arrhythmia,
- pneumonia,
- prolonged air leak,
- chylothorax,
- pulmonary oedema,
- bronchopleural fistula.
What is the prognosis with lung cancer?
5yr survival based on stage:
- Stage I - 90%
- Stage II - 65%
- Stage III - 41%
- Stage IV - <10%
