Lung Flashcards
What are the types of lung cancer?
Small cell lung cancer
Non small cell lung cancer: Adenocarcinoma Squamous cell carcinoma Large cell Alveolar cell carcinoma
What is the difference between SCLC and NSCLC?
SCLC usually centrally located, more aggressive, treatment usually chemo
NSCLC 85-90% of cancers, can be fast or slow growing
Staging with TNM
Surgical, medical or radiation
What are the characteristics of adenocarcinomas?
Usually more peripheral
Most common type in non-smokers
Precursor is atypical alveolar hyperplasia
Histology shows cancer of bronchial mucosal tissue
Often early mets
Prognosis worse than squamous cell
What are the characteristics of squamous cell carcinoma?
Usually centrally located
Smoking
Cancer of squamous epithelial cells
Slow growing tumour
What are some of the known risk factors for the development of lung cancer?
Tobacco smoking, second hand smoke Radon, asbestos Occupational exposure Personal or FH of LC Personal history of lung disease e.g. COPD, TB Radiation exposure
From what cells do small cell lung cancers originate?
Kulchitsky cells
How does squamous cell lung cancer commonly present?
Bronchial obstruction leading to recurrent infections
Finger clubbing
What are the characteristics of small cell lung cancer?
Small round blue cells on histologic staining, approx twice the size of lymphocytes
Centrally located lesions
Aggressive tumour spreads
More responsive to chemo but poor prognosis
What are the symptoms of lung cancer?
Frequently asymptomatic
When symptomatic, cough, malaise and WL predominate
Fever, malaise, nausea Cough, haemoptysis Features of SVCO, PNS Hoarseness - involvement of recurrent laryngeal Weight loss
What are the signs of lung cancer?
Lymphadenopathy Stridor Wheeze Clubbing Hypertrophic pulmonary osteoarthropathy Signs of pleural effusion
What is hypertrophic pulmonary osteoarthropathy?
Fibrovascular proliferation
Results in periostitis (inflammation of periosteum) of the long bones, arthralgia, clubbing.
Lung cancer - paraneoplastic syndrome or in ovarian or adrenal malignancies
CT scan for diagnosis, NSAIDs for the pain
What are the signs of pleural effusion?
Dull - stony dull percussion
Reduced vocal remits
Reduced breath sounds
What is a Pancoast tumour?
Tumour of the pulmonary apex
Local spread may affect brachial plexus, cervical sympathetic trunk, stellate ganglion, subclavian vein
Can cause Horner’s - sympathetic ganglion
Pain in shoulder, radiates into arm and hand - brachial plexus
Atrophy of muscles of upper limb
Oedema of upper limb
Hoarse voice = recurrent laryngeal
What can be seen on CXR with Squamous cell lung cancer?
Cavitations so a CT is needed to rule out TB
What paraneoplastic syndromes are associated with squamous cell lung cancer?
PTHrP = hypercalcaemia
Ectopic TSH = hyperthyroid
Hypertrophic osteoarthropathy
Which type of lung cancer is most common in non-smokers?
Adenocarcinomas
Why do adenocarcinomas tend to present with fewer symptoms?
They are more likely to be located in the peripheries
What are signs/symptoms of Superior Vena Cava Obstruction?
Early morning headache
Arm and Face Oedema
Jugular distention
Describe the clinical features of lung cancer caused by mets
- Fatigue
- Weight loss
- Night sweats
- Lymph node enlargement (supraclavicular)
- Liver mets- anorexia, mass, jaundice, abdo pain, ascites
- Adrenals- addisons (bronze pigment, hypoglycaemia, postural hypotension, weight loss, GI disturbance, weakness, crises)
- Bone- pathological fractures, bone pain
- Pleura- effusions
- CNS- cord compression, focal neurological signs
Describe the clinical features of lung cancer caused by the primary tumour
- Cough (lasting >3 weeks)
- SOB
- Haemoptysis
- Wheeze
- SVC obstruction (SOB, distended neck veins and JVP, headache/ fullness, blurred vision, odema arms/ face, confusion, syncope)
- Persistent/ recurrent infections
Describe the possible clinical features of lung cancer caused by paraneoplastic syndromes
- Horners syndrome (partial ptosis, unilateral anhidrosis, miosis)
- Clubbing
- Hypercalcaemia
- Anaemia
- SIADH
- Cushings
- Lambert eaton myasthenic syndrome (muscle weakness, fatigue, pain, reduced reflexes, walking difficulty, speech impairment and swallowing problems)
- VTE
- Thrombocytosis
What occurs in hypercalcaemia due to paraneoplastic syndromes?
Due to bony mets
Or tumour secretion of
parathyroid hormone related protein - PTHrP
Calcitriol
When is SIADH seen in lung cancer?
SCLC
Hyponatraemia
In extreme cases cerebral oedema
What is Lambert Eaton syndrome?
Caused by antibodies to voltage gated calcium channels, seen in 1% of SCLC
Proximal and ocular muscle weakness
What is hypertrophic osteoarthropathy?
Thought to be due to fibrovascular proliferation due to accumulation of megakaryocytes
Clubbing
Periostitis of small hand joints and metacarpophalangeal joints
Distal expansion of long bones and painful swollen joints
What is the criteria for a two week wait referral?
Suggestive CXR findings
Unexplained haemoptysis and aged over 40
Those with SVCO or stridor require urgent referral and emergency admission
When should an urgent CXR within 2 weeks be considered in those over 40?
Persistent or recurrent chest infection Clubbing Supraclavicular lymphadenopathy or persistent cervical lymphadenopathy Chest signs indicative of lung cancer Thrombocytosis
Have two of these, or one and ever smoked:
cough, fatigue, SOB
Chest pain, weight loss
Appetite loss
What are the investigations for lung cancer?
Bloods Imaging Bronchoscopy Lung function tests Histology and cytology
What does squamous cell carcinoma commonly secrete?
PTHrp causing hypercalcaemia
What does small cell carcinoma commonly secrete?
ACTH - Cushing’s
ADH - SIADH
What are some differentials for lung cancer and features differentiating it from cancer?
TB - night sweats, sputum culture, cavitating lesion
Mets to lungs from other sites - symptoms related to primary tumour
Sarcoidosis - enlarged parotids, erythema nodosum, granulomas
Wegener’s - cANCA, saddle nose deformity, urinalysis
Non-Hodgkin’s - night sweats, hepatosplenomegaly
What are appropriate bedside investigations?
Pulse oximetry - aim for 94-98%
ECG performed pre-operatively
What are appropriate lab investigations?
FBC - anaemia
LFTs - raised ALP, GGT hepatic mets, raised ALP bone mets
U&Es
Serum calcium, bone profile
What is appropriate imaging investigations?
CXR - opacities, pleural effusion or lung collapse
CT chest-abdomen-pelvis
Bronchoscopy and biopsy - confirms subtype, presence of targetable mutations
PET-CT for staging
CT/MRI brain can be ordered to exclude cerebral mets
How can tissue biopsies be obtained?
Bronchoscopy
Image guided biopsy
Video assisted thoracoscopic surgery
Mediastinoscopy
How can cytology be obtained?
Aspirates, washings, pleural fluid
Obtained from the tumour, lymph node or mets
What is the TNM staging?
Tumour
TX: Primary tumour cannot be assessed or tumour proven by presence of malignant cells in sputum or bronchial washings but not visualised by imaging or bronchoscopy
T0: No evidence of a primary tumour
Tis: Carcinoma in situ
T1: Tumour measuring 3 cm or less in greatest dimension surrounded by lung or visceral pleura without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e. not in the main bronchus)
T1a: tumor ≤1 cm
T1b: tumor >1 cm but ≤2 cm
T1c: tumor >2 cm but ≤3 cm
T2: Tumour > 3 cm but ≤ 5 cm or tumour with any of the following features:
Involves the main bronchus regardless of distance from the carina but without the involvement of the carina
Invades visceral pleura
Associated with atelectasis or obstructive pneumonitis that extends to the hilar region involving part or all of the lung
T2a: tumour > 3 cm but ≤ 4 cm in greatest dimension
T2b: tumour > 4 cm but ≤ 5 cm in greatest dimension
T3: Tumour > 5 cm but ≤ 7 cm in greatest dimension or associated with separate tumour nodule(s) in the same lobe as the primary tumour or directly invades any of the following structure:
Chest wall (including the parietal pleura and superior sulcus)
Phrenic nerve
Parietal pericardium
T4: Tumour > 7 cm in greatest dimension or associated with separate tumour nodule(s) in a different ipsilateral lobe than that of the primary tumour or invades any of the following structures: diaphragm, mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, oesophagus, vertebral body or carina)
Node
Nx: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastasis
N1: Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary nodes, including involvement by direct extension
N2: Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s)
N3: Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s)
Metastasis
M0: no distant metastasis
M1: distant metastasis present
The above tumour, node and metastasis classification can then be grouped into stages:
Stage I:
IA: T1N0M0
IIB: T2aN0M0
Stage II:
IIA: T2bN0M0
IIB: T1N1M0, T2N1M0, T3N0M0
Stage III:
IIIA: T1N2M0, T2N2M0, T3N1M0, T4N0M0, T4N1M0
IIIB: T1N3M0, T2N3M0, T3N2M0
IIIC: T3N3M0, T4N3M0
Stage IV: Any T, Any N, M1
What is the I-IV cancer staging system?
I: One small tumour (<4cm) – localised to one lung
II: Larger tumour (>4cm) – may have spread to nearby lymph nodes
III: Tumour that has spread to contralateral lymph nodes, or grown into nearby structures (e.g. trachea)
IV: Tumour that has spread to lymph nodes outside the chest, or other organs (e.g. liver)
What is the management of Stage I-III NSCLC?
Surgery - lobectomy/pneumonectomy in patients with intact lung function
or wedge resection if reduced lung function e.g. elderly
Pre-op chemo, post op chemo/radiotherapy
Pneumonectomy is where an entire lung is removed
What is SABR?
Stereotactic ablative radiotherapy
If unsuitable for surgery e.g. too frail
Directs more intense and focused beam of radiation at the tumour
Reduces number of sessions needed and minimises damage to surrounding tissue
What is the management of Stage IV NSCLC?
Targeted therapy - drugs target mutations
Immunotherapy - targets immune checkpoints
Chemotherapy
Palliative care - radiotherapy for mets and symptom control
What are some examples of targeted therapy for NSCLC?
EGFR-TK - Gefitinib, Osimertinib
(epidermal growth factor receptor tyrosine kinase)
ALK - Alectinib
(Anaplastic lymphoma kinase positive gene rearrangement)
ROS1 - Crizotinib
What are examples of immunotherapy?
Immune checkpoint PD-L1 is targeted by pembrolizumab
What is the basis of lung cancer pathogenesis?
Initiation - due to exposure to a carcinogen, DNA damage leads to permanent mutation
Promotion - subsequent or continued exposure, growth, proliferation and development into a tumour
Progression - undergoes changes causing morphological changes and malignant features
What is the staging of small cell lung cancer?
Limited disease - cancer is only present in one side of the chest in a radioencompassable volume (single radiation treatment field)
Extensive disease - cancer is present bilaterally in the chest, there is pleural effusion or there are distant metastases
What are indicators of a good outcome post surgery?
Lung function tests done to assess lung reserve
FEV1 greater than or equal to 1.2 and diffusing capacity of the lung for CO greater than 60% predicted
Fit for surgery with FEV 0.7
What are some of the indications for chemo?
Shrink tumour prior to surgery or radiation
Kill cancer cells not removed during surgery, to reduce risk of recurrence
Primary treatment for those unable to have surgery
Relieve pain of advanced cancer
Maintenance therapy for those with advanced cancer that is responsive to chemo
How can lung cancer cause anaemia?
Similar mechanism to anaemia of chronic disease: tumour causes macrophage activation, causing hepcidin release (directly and via cytokines acting on liver this reduces iron absorbtion and release from stores, idea is to starve bacteria in blood of iron) leading to functional iron deficiency
How can lung cancer cause VTE?
Inflammatory cytokines activate procoagulant pathways.
Ca cells can also produce procoagulant proteins, fibrinolysis inhibitors and microparticles also
What is the prognosis of SCLC?
Limited stage - 18-30 months
Extensive - 7-12 months
What are indications for adjuvant chemotherapy?
Potentially curative resection
Final pathological stage of 2 or 3
Good post-op recovery
No co-morbidities precluding chemo
What are the symptoms of Pancoast tumour?
Associated with non small cell lung cancer
Compression of brachiocephalic vein, subclavian artery, phrenic nerve, vagus nerve, recurrent laryngeal, sympathetic ganglion
Symptoms of lung cancer
Pain/weakness in muscles of arm and hand
Hoarse voice, bovine cough
SVCO
What is Carcinoid syndrome?
Paraneoplastic syndrome
Occurs secondary to carcinoid tumours
Flushing, diarrhoea - due to serotonin, histamines and gastrin, heart failure, vomiting, bronchoconstriction, abdo pain due to hepatomegaly
Endogenous secretion of serotonin and kvllikrein
Where is it important to examine upon investigating lung cancer?
Check axillary lymph nodes when suspecting lung cancer as metastasise to here early
What is the treatment of SCLC?
Nearly always metastasised, so palliative care with chemo
Regimens include
cyclophosphamide, doxorubicin, vincristine and etoposide or
cisplatin and radiotherapy
What is a common chemotherapy treatment regimen?
Gemcitabine and Carboplatin - GemCarbo
Bloods taken beforehand
Anti-emetics given
Each cycle takes 21 days/3 weeks:
Day 1 - gemcitabine and carboplatin
Day 8 - gemcitabine only
Then rest period of no treatment for 13 days
Then begin next cycle, pts tend to have 4 cycles
What is a performance assessment for chemotherapy?
Lower the number = fitter
0 - fit and active
1 - fit and active but unable to work, e.g. cannot do manual labour job
2 - not working, but able to be up and about for 50% of the day and self-care
3 - able to self care, but up and active for less than 50% of the day
4 - bed bound
What are complications of surgical management?
Pneumonia
Atelectasis
Chylothorax - lymphatic fluid from the thoracic duct in the pleuritic cavity
Post-op haemorrhage leading to haemothorax
Pneumothorax
Bronchial stump insufficiency
Mediastinal shift
What is prophylactic cranial irradiation?
Combat occurrence of mets, e.g. from SCLC
Either highly precise or therapeutic radiation
What are carcinoid tumours?
Slow growing type of neuroendocrine tumour originating in cells of the neuroendocrine system
In the lung - is an uncommon low-grade malignant lung mass, typically present with cough or haemoptysis
What biomarkers are used to detect carcinoid tumours?
Chromogranin A and 5HIAA levels
How are carcinoid tumours managed?
-Surgery + adjuvant chemo is curative if localised but mets common at presentation so surgery often palliative
- type of surgery depends on location of the tumour
-
Somatostatin analogues like octreotide can give symptom control if functional tumour
interferon alpha inhibits protein, hormone synthesis and angiogenesis and stimulates immune system- is primary treatment for low proliferating tumours
cytotoxic chemo for high proliferating tumours and large tumour burden
radiotherapy only used if brain or bone mets
List some common causes of pneumonitis in patients undergoing treatment for lung cancer.
Radiation therapy
Chemotherapy
Viral infection
Bronchial obstruction
What is radiation pneumonitis?
Loss of epithelial cells
Oedema, inflammation
Occlusion of airways
Fibrosis
What is the presentation of pneumonitis?
History of precipitating cause
SOB, cough, burning sensation
Fatigue, cyanosis, clubbing
What are the investigations for pneumonitis?
Bloods - FBC, raised ESR and CRP Blood gases - hyperaemia Sputum cultures Serum precipitating antibodies CXR may be normal or may show micro nodular or reticular opacities CT scan Pulmonary function tests Lung biopsy
What are the complications of pneumonitis?
Recurrent pneumonia Pneumothorax Pulmonary fibrosis Cor pulmonale COPD
What is the management of pneumonitis?
Use of corticosteroids e.g. short course of oral prednisone or methylprednisolone
What is a pleural effusion?
Accumulation of fluid in the pleural space - between the visceral and parietal pleura
Serous fluid within pleural membrane allows these to slide over each other and create surface tension
What is the classification of pleural effusion?
Transudative - <25g/l
Exudative - high protein level of >35g/L due to increased permeability
What are the causes of transudative pleural effusion?
Heart failure, liver failure
Hypoalbuminaemia, nephrotic syndrome, dialysis
What are the causes of exudative pleural effusion?
Infection - parapneumonic, TB, malignancy
What are other types of pleural effusion?
Haemothorax - blood in pleural space
Empyema - pus in pleural space
Chylothorax - chyle in pleural space due to disruption of thoracic duct e.g. neoplasms, trauma
What are the clinical features of pleural effusion?
Small - asymptomatic
Breathlessness
Cough
Pleuritic chest pain
Check for symptoms of cancer, heart failure, infection, smoking history, asbestos exposure
What is looked for on examination for pleural effusion?
Peripheral inspection
Reduced chest movement
Tracheal deviation away from affected side
Reduced tactile remits over pleural effusion
Stony dull on percussion
Breath sounds and vocal resonance reduced
What are the differentials for pleural effusion?
Infection; pneumonia, TB
Malignancy without effusion
Pulmonary embolism
Pneumothorax
What are the investigations for pleural effusion?
Bedside
ECG, urine dip for protein
Bloods
FBC, CRP, cultures - infection
ABG, d-dimer (PE?)
LFTs U&Es, amylase TFTs
CXR
Unilateral - exudative
Bilateral - transudative
Look for consolidation, malignancy, cardiomegaly, pleural plaques (asbestos)
CT, ECHO
If thought to be exudative - pleural fluid aspiration under USS guidance
What is Light’s criteria summary?
The fluid is an exudate if one or more of the following criteria are met:
Pleural fluid protein divided by serum protein is >0.5
Pleural fluid LDH divided by serum LDH is >0.6
Pleural fluid LDH is >⅔ the upper limit of the laboratory normal value for serum LDH
What is the management of pleural effusion?
Treat underlying cause
Diuretics heart failure
Antibiotics for infection
Therapeutic aspiration
Chest drain insertion
Long term indwelling chest drain
Pleurodesis - mildly irritant drug into pleural space to stick lung to wall of chest
Video assisted thoracic surgery
What are some complications of pleural effusion?
In parapneumonic effusions, complications include empyema and sepsis
What is a mesothelioma?
Malignant growth of mesothelial cells
Most commonly affecting the pleura
Strongly associated with prior exposure to asbestos
Mesothelial cells line the body cavities e.g. pleura, peritoneum, pericardium, testis
What can cause the development of mesothelioma?
Secondary to asbestos exposure; shipbuilding, mining, plumbing, manufacturing
Germline mutations in BAP1, NF2 genes
What is the pathophysiology of mesothelioma?
Asbestos fibres inhaled deeply into the lung
Penetrate the pleural space
Provoke persistent inflammatory reaction with mesothelial cells
Parietal pleura affected
What is the presentation of mesothelioma?
Pleural - progressive dyspnoea, chest wall pain
Chronic cough, malaise, fever, chills, weight loss
Peritoneal - abdo swelling, pain due to ascites, WL, fever, chills etc
Pericardial - chest pain, cough, orthopnoea, dyspnoea
How can a mesothelioma be diagnosed?
CT scan
Shows pleural thickening, effusion or pneumothorax
Pleurocentesis - exudative pleural effusion, cytology
Biopsy - thoracoscopy or laparoscopy shows mesothelioma cells and psammoma bodies (calcium)
Immunohistochemistry markers
What is the management of mesothelioma?
Generally resistant to radio and chemo
Surgical resection
Symptomatic treatment
Survival 8-14 months
What are the signs of mets?
Liver - abdo pain, nausea, early satiety
Brain - behavioural changes, aphasia, neurological deficits, nausea, vomiting, seizures
Bone - pain, pathological fractures
What are the differentials for lung cancer?
PE TB Pneumonia Histoplasmosis Sarcoidosis - inflammatory condition, non caveating granulomas in organs COPD Mesothelioma
