Lung Cancer Flashcards
What are the most common symptoms of lung cancer?
Persistent cough
Hemoptysis (bleeding from the tumour)
Chest pain (pleuritic / central)
If peripheral tumor –> invade into pleural/chest wall –> pleuritic pain
If central mass (eg: bronchial tumor) –> dull central pain
Dyspnoea from:
- Airway obstruction
- Phrenic N involvement
- Malignant pleural effusion
- Pneumonia, Lobar collapse, atelectasis
What are the risk factors for lung cancer?
- Smoking
- Marijuana and cocaine smoking
- Radiation therapy
- Environmental toxins (asbestos, arsenic, chromium, petroleum products, tar)
- Pulmonary fibrosis
- History of malignancy (could be mets to lung)
- Family history of CA
What are the signs of lung cancer (general)?
- Haemoptysis
- Clubbing (sometimes with hypertrophic pulmonary osteoarthropathy)
- Malignant effusion (unilateral, can cover underlying tumor)
- Tender ribs (secondary deposits)
- Supraclavicular or axillary lymphadenopathy
- Paraneoplastic syndrome (e.g. SIADH, hypercalcemia (from PTHrP), Cushings, carcinoid syndrome, Lambert-Eaton myasthenic syndrome)
What are the local signs specific to bronchial/ tracheal tumours?
Wheeze/Stridor and progressive Dyspnoea
Reduced inspiratory flow –> Atelectasis / Lobar Collapse
- Collapse is caused by luminal blockage of airways – tumor, infection, foreign body
- Or can be extraluminal tumor pressing onto the airway
Post obstructive pneumonia: obstruction causes accumulation of secretions –> infection
Mediastinal compression (dull central pain + signs of phrenic nerve involvement ↓) - Wheeze/Stridor for tracheal upper/lower airway obstruction
SVC obstruction: in centrally located CA (fullness in head, dyspnoea, dilated neck and chest veins, plethoric appearance)
Recurrent laryngeal nerve compression – Hoarseness of voice
Involvement of phrenic Nerve: paralysis of ipsilateral hemidiaphragm
Oesophageal involvement: progressive dysphagia
Pericardial Involvement: pericardial effusion and malignant dysrhythmias
Pancoast syndrome (pain in UL, Horner’s syndrome, atrophy of hand muscles from C8-T1 nerve root lesion)
- Aka tumor at apex of lung –> compresses onto brachial plexus + symp chain –> Horner’s Syndrome
- C8/T1 palsy = Muscle atrophy of hand; Weakness & Pain radiating down the arm
- Horner’s Syndrome = miosis, ptosis, anhidrosis
How does SVC syndrome present?
Presents w:
- Dyspnoea and/or dyaphagia
- Stridor
- Venous congestion in the neck + dilated veins in the upper chest and arms
- Causing swollen, oedematous facies and arms
How is SVC syndrome treated?
Treatment:
- Immediate steroids, vascular stents, anticoagulation & mediastinal radiotherapy or chemotherapy.
- Ventilatory support may be required until treatment has had time to relieve the obstruction.
HOWEVER: Some tumors (eg: lymphomas, small-cell lung cancers & germ cell tumours) are so sensitive to chemotherapy (Tumor Lysis Syndrome due to high turnover rate) that SVC syndrome is preferred to radiotherapy!
What are the clinical features seen in lung cancer metastases?
Lungs typically will mets to – bone, brain, liver, (contralateral) lung, adrenals (usually does NOT mets to below the adrenals!)
Liver
- Anorexia
- Nausea
- Weight loss
- Liver capsular pain (RUQ radiating across the abdomen)
Adrenals (40% of mets occur in the adrenals!)
- Asymptomatic (generally adrenal metastasis does NOT lead to adrenal insufficiency)
Bone
- Bone pain
- Pathological fractures
- Spinal cord compression if spine is involved (requires urgent treatment)
- Brain
- SOLs (space occupying lesions) causing mass effect and raised ICP
- Uncommonly: carcinomatous meningitis, cranial nerve defects, headache, confusion
Malignant pleural effusion
- SOB
- Pleuritic pain
What is the relevant hx to ask in a patient with suspected lung cancer?
Local symptoms: LOW, LOA, Dyspnoea, Cough, Haemoptysis, Chest pain
Regional Symptoms
- Esophagus: Dysphagia
- Trachea: SOB
- RLN: Hoarseness of voice
- Pancoast: BOV, Weakness / pain / paraesthesia in the hand
Metastatic symptoms
- Lung: to the C/I lung nothing to ask, but note that this is considered mets!
- Liver: RUQ pain, yellowing of skin, ABCDE
- Bone: Bone pain
- Brain: BOV, headache, N&V, worsens on straining and in the morning
Paraneoplastic symptoms (is +/-)
- Cushing’s Syndrome
- Hypercalcaemia: abdo pain, urinary stones, increased urination, pancreatitis
As well as:
- Smoking history
- FHx of lung cancer / other cancers
- PMH of other cancers
What are the investigations to be done in a patient with suspected lung cancer?
FBC, UECr, Electrolytes (Na, Ca)
Chest X-ray
CT Thorax w contrast (important)
- Preferred over MRI
- Helps visualise tumor and its complications
- Helps guide BIOPSY! i.e. different methods depending on location of tumor
Biopsy
- Central / Bronchial tumor: Bronchoscopy w/ EBUS (Endobronchial US) guided TBNA (Trans-bronchial needle aspiration)
- Peripheral tumor: Percutaneous aspiration and biopsy Or Bronchoscopy + EBUS guided TB LN Biopsy (TBLB)
Staging scans
- CT TAP +/- PET Scan –> TNM Staging
- Investigation of choice for characterising extent of mediastinal nodal involvement and highlighting distant metastases either not visualised or indeterminate on CT.
- Most commonly PET images are combined with CT for best correlation
MRI
- MRI is NOT USEFUL for the diagnosis of a primary lung tumour other than in Pancoast tumours with nerve invasion or when assessing for chest wall involvement prior to surgery
- Perform MRI brain only if symptomatic
What are the features of malignancy on CXR?
Locate lesion
- lesion only visible if >1cm
- Speculate, cavitating or smooth edged
Pleural involvement:
- malignant effusion,
- usually unilateral
- commonly large which can cause obscuration of an underlying mass or pleural tumour
- mesothelioma is a ddx
- Intrathoracic metastases (cannonball lesions or miliary picture)
Mediastinal widening –> causing mass lesion (usually due to hilar lymphadenopathy)
- splayed carina
- hilar enlargement
- Paratracheal shaddowing
Lymphangitis carcinomatosa (reticular opacities)
- Carcinoma spreads through lymphatic channels
In bronchiall carcinoma this is usually unilateral and associated with striking dypsnea
- bilateral lymphagitis should prompt investigation for a primary site other than lung, such as breast/ stomach/ colon
Collapse
- endoluminal tumour causes complete collapse of the lung and associated mediastinal shift OR
- collapse of a lobe or segment resulting in volume loss on the affected side with raised hemidiaphragm/ deviated trachea
Persistent consolidation
- tumour cause partial obstruction of a bronchus
- this results in retention of secretions, bacterial over growth and subsequent infection
However, may miss if tumor is too small / located near clavicles, behind heart, around diaphragm
What are the 5Cs that small cell carcinoma are associated with?
- Scanty cytoplasm
- Smoking cigarettes
- Highly sensitive to Chemotherapy due to high proliferating rate but high risk of tumour lysis syndrome if started on chemotherapy
- Seldom has clubbing (<3%)
- Centrally Located – central region of the lung
What is the histological features of small cell carcinoma?
- Scant cytoplasm, ill-defined borders and finely granular nuclear chromatin
- High mitotic count, cells grow in clusters without glandular or squamous organization, necrosis common
What are the genetic mutations in small cell carcinoma?
Associated with loss-of-function aberrations
- TP53 (aka p53) mutation in 60-90%
- Retinoblastoma tumour suppressor in almost 100%
- Chromosome 3p deletions
Also associated with MYC gene amplification
What paraneoplastic syndromes can small cell carcinoma cause?
Can produce
- ACTH (Ectopic adrenocorticotropin /Cushing’s syndrome)
- ADH (SIADH)
Associated with Lambert-Eaton myasthenic syndrome –> proximal muscle weakness that IMPROVES w/ repeated use
What is the patient group that normally get adenocarcinoma?
Most common in non-smoking, young Asian women (or light smoker <10pys)
What are the morphological features of adenocarcinoma?
Originates from mucinous glandular cells –> will have glandular acinar appearance
- Discrete, cluster and glandular pattern
- Round cells with moderate vacuolated cytoplasm
- Central to eccentric nucleus with vesicular chromatin and prominent nucleoli
What are the genetic mutations in patients with adenocarcinoma?
Receptor tyrosine kinases mutation (EGFR, ALK, ROS, c-MET)
• ALWAYS check for EGFR, ROS1, ALK mutation – these mutations are common in NSCLC, esp adenocarcinoma –> up to 6y survival c/f 1y for chemo/RT
• If present –> can give
TKIs (Tyrosine Kinase Inhibitors) targeted Tx
Majority express thyroid transcription factor-1 (TTF1) required for normal lung development and CK7+ve
- CK7+ and TTF1+ together = highly indicative of adenocarcinoma of the lung
What are the 6Cs associated with squamous cell carcinoma?
- Central
- Clubbing
- Cigarettes
- Cavitatory lesions
- Calcium is high (PTHrp)
- Collapse of lung: Mass may obstruct the lumen of the major bronchus and produce distal atelectasis and infection (post-obstructive pneumonia)
What are the histological features of squamous cell carcinoma?
well differentiated squamous cell neoplasms with keratin pearls and intercellular bridges
What are the genetic mutations in patients with squamous cell carcinoma?
Associated closely with chromosomal deletions involving tumour suppressor loci
- CDKN2A gene (3p, 9p) inactivation and loss of p16
- TP53 (17p) mutation seen in ~90% of squamous cell carcinomas
- Retinoblastoma tumour suppressor inhibition
What are the paraneoplastic syndromes associated with squamous cell carcinoma?
Associated with hypercalcemia due to PTHrp secretion
Associated with Lambert-Eaton myasthenic syndrome
What is the morphology of large cell carcinoma?
- Forms sheets of large cells without clear borders, alike merging together
- They have prominent nucleoli
- Need to improve on this section!
How do secondary tumours present on CXR?
- Usually present as round shadows, early mets
However, if the metastasis present as a SOLITARY round shadow
- Usually renal cell carcinoma
How does lymphagitis carcinomatosis present on CXR?
bilateral lymphadenopathy w streaky basal shadowing fanning out over both lung fields. There is septal thickening as the lymphatics follow the septum
What are the relative c/is to remove the lung tumour?
Poor lung reserve e.g. COPD: Do a full lung function test with transfer capacity
Weak heart / CV disease
- Do cardiopulmonary exercise testing
- Stress echo
- Or preoperative angiography
Old age
What is role of surgery in lung cancer patients?
Surgery for CURE
Tumour and nearby lymph nodes removed to offer best chance of cure
For early stage NSCLC (Stage I, II, IIIA), lobectomy shown to be most effective
- For Stage IIIA: chemoradiation is first done to “downstage” the disease
- If nodal involvement exists, patients require adjuvant chemotherapy on top of surgical resection
What is role of radiation therapy in lung cancer patients?
For pts with high lung capacity + early stage NSCLC
- Preferred over Surgery in patients with Cardiopulmonary comorbidities!
- Use of high-energy x-rays or particles to destroy cancer cells
Pain, invasion, haemoptysis, SVC syndrome all respond favourably to radiation therapy
What are the side effects of radiation therapy?
fatigue, malaise, loss of appetite, skin irritation at treatment
What are the complications of radiation therapy?
Radiation pneumonitis – irritation and inflammation of lung (occurs in 15% pts)
- Dyspnoea + Dry Cough
- Essentially pneumonia without the consolidation
Radiation Fibrosis (fibrotic change happening ~1year after therapy) - Hence important for radiation treatments to avoid healthy part of lungs
What is role of chemotherapy in lung cancer patients?
- May be prescribed before or after surgery, or before, during or after radiation therapy to consolidate treatment!
- Can improve survival and lessen lung cancer symptoms in all patients, even those with widespread lung cancer
What are the mutations to screen in NSLC? What are the relevant drugs that target them?
** When dealing with NSCLC we must ALWAYS screen for mutations: EGFR, ALK and ROS1 – these are all RTK mutations. These 3 mutations are commonly found in NSCLC, especially adenocarcinoma! The reason is because there is effective targeted treatment for CA expressing these mutations –> allows better more effective treatment of CA
- EGFR mutation (in particular point mutation L858R) we can give Erlotinib
- For ROS1 or ALK mutation, we can give Crizotinib
