Lung Cancer Flashcards

1
Q

What are the most common symptoms of lung cancer?

A

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
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2
Q

What are the risk factors for lung cancer?

A
  • 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
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3
Q

What are the signs of lung cancer (general)?

A
  • 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)
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4
Q

What are the local signs specific to bronchial/ tracheal tumours?

A

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
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5
Q

How does SVC syndrome present?

A

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
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6
Q

How is SVC syndrome treated?

A

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!

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7
Q

What are the clinical features seen in lung cancer metastases?

A

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
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8
Q

What is the relevant hx to ask in a patient with suspected lung cancer?

A

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
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9
Q

What are the investigations to be done in a patient with suspected lung cancer?

A

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
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10
Q

What are the features of malignancy on CXR?

A

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

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11
Q

What are the 5Cs that small cell carcinoma are associated with?

A
  • 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
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12
Q

What is the histological features of small cell carcinoma?

A
  • Scant cytoplasm, ill-defined borders and finely granular nuclear chromatin
  • High mitotic count, cells grow in clusters without glandular or squamous organization, necrosis common
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13
Q

What are the genetic mutations in small cell carcinoma?

A

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

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14
Q

What paraneoplastic syndromes can small cell carcinoma cause?

A

Can produce

  • ACTH (Ectopic adrenocorticotropin /Cushing’s syndrome)
  • ADH (SIADH)

Associated with Lambert-Eaton myasthenic syndrome –> proximal muscle weakness that IMPROVES w/ repeated use

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15
Q

What is the patient group that normally get adenocarcinoma?

A

Most common in non-smoking, young Asian women (or light smoker <10pys)

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16
Q

What are the morphological features of adenocarcinoma?

A

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
17
Q

What are the genetic mutations in patients with adenocarcinoma?

A

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

18
Q

What are the 6Cs associated with squamous cell carcinoma?

A
  • 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)
19
Q

What are the histological features of squamous cell carcinoma?

A

well differentiated squamous cell neoplasms with keratin pearls and intercellular bridges

20
Q

What are the genetic mutations in patients with squamous cell carcinoma?

A

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
21
Q

What are the paraneoplastic syndromes associated with squamous cell carcinoma?

A

Associated with hypercalcemia due to PTHrp secretion

Associated with Lambert-Eaton myasthenic syndrome

22
Q

What is the morphology of large cell carcinoma?

A
  • Forms sheets of large cells without clear borders, alike merging together
  • They have prominent nucleoli
  • Need to improve on this section!
23
Q

How do secondary tumours present on CXR?

A
  • Usually present as round shadows, early mets

However, if the metastasis present as a SOLITARY round shadow
- Usually renal cell carcinoma

24
Q

How does lymphagitis carcinomatosis present on CXR?

A

bilateral lymphadenopathy w streaky basal shadowing fanning out over both lung fields. There is septal thickening as the lymphatics follow the septum

25
Q

What are the relative c/is to remove the lung tumour?

A

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

26
Q

What is role of surgery in lung cancer patients?

A

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
27
Q

What is role of radiation therapy in lung cancer patients?

A

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

28
Q

What are the side effects of radiation therapy?

A

fatigue, malaise, loss of appetite, skin irritation at treatment

29
Q

What are the complications of radiation therapy?

A

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
30
Q

What is role of chemotherapy in lung cancer patients?

A
  • 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
31
Q

What are the mutations to screen in NSLC? What are the relevant drugs that target them?

A

** 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