Lung Cancer

On my respiratory firm I met a 64 year old gentleman who presented with a 2 month history of pain along his right arm. It spread from his shoulder blade up to his proximal forearm. Within 1 month, he lost use of the arm due to the pain. He described the pain as ‘agony’ and rated it 20/10. Additionally, there was a large, warm, solid palpable mass on his right upper chest wall, which had gradually grown in size. He also reported night sweats, a loss of appetite over this 2 month period and 1 stone of weight loss. There was no cough, shortness of breath or chest pain. He had a past medical history of depression, lumbar spinal damage, annual bronchitis and an appendectomy. He took no regular medications but was on morphine during his admission.

His family history was significant for recurrent bronchitis and emphysema, his father had an MI, mother had skin cancer and brother had cancer in his tongue. He was a current smoker with a 43 pack year history. He drank about 14 units of alcohol a week, and had previously struggled with alcohol dependence over a 14 year period. He was living in a hostel and had been homeless for the past 8 years, half of that time period spent living in the streets.

This man had terminal lung cancer, presenting with non-respiratory symptoms. The tumour was invading the chest wall and also invading the brachial plexus, causing his pain.


Lung Cancer

Definition: primary malignant neoplasm of lung

Mostly bronchogenic carcinomas, classified histologically:

Squamous cell carcinoma (35%)

Adenocarcinoma (27%)

Small cell carcinoma (20%)- Very aggressive, fast growing tumour. Fastest doubling time.

Large cell (10%)

Other carcinomas: including- alveolar cell carcinoma (< 1%), adenoid cystic carcinoma, malignant carcinoid tumour

Other lung tumours (rare): bronchial adenoma (slow growing), hamartoma (benign), mesothelioma

Although some types are associated with suggestive presentations, clinical manifestations are never specific enough to be able to determine the cell type. Needs to be confirmed on biopsy as management varies accordingly.

Aetiology/ risk factors:

90% of lung cancer can be attributed to smoking

Smoking rates are higher in lower socioeconomic groups, roughly equal between the sexes

Occupational and environmental factors e.g. exposure to naturally occurring radon, asbestos, chromium, arsenic, iron oxides, radiation also contributes

-Tumours generally arise in main or lobar bronchi. Adenocarcinomas tend to occur more peripherally.

Epidemiology:

Carcinoma of the bronchus accounts for ~19% of all cancer and 27% of cancer deaths (40,000 cases/yr in UK)

Lung cancer is the 3rd most common cancer in the UK (2014), 2nd most common in males and in females. It is by far the top cause of cancer death in the UK.

Incidence increasing in women

Many possible presentations of lung cancer. May present with one of the many complications (see extensive complications section).

Symptoms:

Systemic symptoms: general malaise, lethargy, anorexia, weight loss, depression

Primary lesion: cough (80%), change in character of longstanding cough, haemoptysis (70%), breathlessness (60%), chest pain (40%), recurrent or slowly resolving pneumonia

Signs:

Systemic: cachexia

Primary lesion: pneumonia- consolidation (dull percussion note, ↑ vocal resonance)

lobar collapse signs- (tracheal deviation, reduced breath sounds)

fixed, monophonic wheeze

Other: anaemia, clubbing, hypertrophic osteoarthropathy, lymphadenopathy (supraclavicular or axillary)

Investigations:

Chest x-ray:

-peripheral nodule (Coin lesions)

 

Image result for chest x-ray lung cancer coin lesion

Spot the coin lesion…

 

Image result for chest x-ray lung cancer

If all chest x-rays came labelled like this…

 

-widened mediastinum/ hilar enlargement due to mediastinal lymphadenopathy

-consolidation, lung collapse (due to obstruction of bronchi by cancer), pleural effusion

Golden S-sign (reverse S at the lower margin of the collapsed right upper lobe)- typically seen with right upper lobe collapse. Created by a central mass obstructing the upper lobe bronchus e.g. carcinoma, metastasis, enlarged lymph nodes. Also, note the tracheal deviation towards the collapsed lobe

-raised hemidiaphragm due to loss of volume in lobar collapse or phrenic nerve damage by tumour

-bony metastases

-features of lymphangitis carcinomatosis (= diffuse infiltration and obstruction of pulmonary parenchymal lymphatic channels by tumour. 80% caused by adenocarcinoma. CXR: reticulonodular opacification. Best seen on CT. Very poor prognosis.)

Cytology- sputum and pleural fluid

Bronchoscopy with brushings or biopsy- give histology and assess operability +/- endobronchial ultrasound for assessment and biopsy

-visualise endobronchial tumours, extrinsic compression by malignant lymphadenopathy

Fine needle aspiration or biopsy -of peripheral lesions and superficial lymph nodes

CT thorax (+ abdomen)– determine extent of tumour, stage tumour, guide bronchoscopy

18F-deoxyglucose PET or PET /CT scanning- PET scan can be helpful when there is doubt about the activity or nature of a shadow seen on CT. Help in staging.

Radionuclide bone scan– if suspected metastasis, for staging

CT brain- if suspected metastasis, for staging

Lung function testing- help assess suitability for lobectomy

Bloods– FBC (anaemia?), U&Es (SIADH?), Ca (hypercalcaemia?), Alkaline Phosphate (↑ in bone mets), LFTs

TNM Staging for non-small cell lung cancer:

Primary tumour (T)

TX-malignant cells in bronchial secretions, no other evidence of tumour

TIS- carcinoma in situ

T0- none evident

T1- 3 cm, in lobar or more distal airway

T2- 3 cm and > 2cm distal to carina

or pleural involvement

or obstructive pneumonitis extending to hilum, but not all lung

T3- involves chest wall, diaphragm, mediastinal pleura, pericardium

or < 2cm from, but not at, carina 

tumour > 7 cm diameter and nodules in same lobe

T4- involves mediastinum, heart, great vessels, trachea, oesophagus, vertebral body, carina, malignant effusion, or nodules in another lobe

Regional nodes (N)

N0– none involved (after mediastinoscopy)

N1- peribronchial and/ or ipsilateral hilum

N2- ipsilateral mediastinum or subcarinal

N3- contralateral mediastinum or hilum, scalene or supraclavicular

Distant metastasis (M)

M0– none

M1a- nodule in other lung, pleural lesions, or malignant effusions

M1b- distant metastases present

Stages

Occult-TX/N0/M0

I- TIS/T1/T2  N0  M0

II- T1/T2  N1  M0  or  T3  N0  M0 

IIIa- T3  N1  M0  or  T1/T2/T3  N2  M0

IIIb- T1/T2/T3/T4  N3  M0  or  T4  N0/N1/N2  M0

IV- T1/2/3/4  N0/1/2/3  M1

Management:

Treatment options include surgery, radical radiotherapy, chemotherapy and palliation of symptoms.

Non-small cell lung cancer:

Stage 1 and 2 (peripheral, no metastatic spread)=

→ surgical excision if patient fit with good lung function

→ alternatively, radical radiotherapy with curative intent

Stage 3 & 4 (more advanced) = palliative treatment of symptoms, extend life

→ chemotherapy (IV/ oral) +/- radiotherapy (external beam, endobronchial)

e.g. Cetuximab

Small cell lung cancer: nearly always disseminated at presentation

→ Chemotherapy (most chemosensitive type, but invariably relapse)

                           = Cyclophosphamide + doxorubicin + vincristine + etoposide

                           = Cisplatin +/- radiotherapy (if limited disease)

→ If chemo achieves good shrinkage → consider consolidative radiotherapy

→ May give prophylactic cranial radiotherapy

 

Palliative services should be available from the moment the disease is diagnosed.

Radiotherapy- for bronchial obstruction, SVC obstruction, haemoptysis, bone pain, cerebral metastasis

SVC stent + radiotherapy + dexamethasonefor SVC obstruction

Endobronchial therapy: tracheal stenting, cryotherapy, laser, brachytherapy (radioactive source placed close to tumour)

Pleural drainage/ pleurodesis– for symptomatic pleural effusions

Drugs: analgesia, steroids, antiemetics, cough linctus (codeine), bronchodilators, antidepressants

Complications:

Patient may present with the complications of lung cancer:

Local spread:

Apical spread

-Involving brachial plexus, presenting with pain or weakness down arm, wasting of small hand muscles = Superior sulcus or Pancoast’s syndrome (this is what the case at the start was)

-Sympathetic chain involvement = Horner’s Syndrome = ptosis, miosis and anhydrosis

Image result for horner's syndrome

Lateral spread:

Pleural effusion (stony dull percussion note, reduced breath sounds)

-Pleuritic chest pain

-Chest wall invasion (visible painful swelling), rib destruction

Lymph node spread: Palpable lymphadenopathy in the cervical and supra-clavicular fossae-  axillary nodes if chest wall involvement.

Central spread:

Atrial involvement/ atrial fibrillation = palpitations, faintness, irregularly irregular pulse

Pericardial effusion, pericarditis

-Stridor

Oesophageal compression = dysphagia

Superior vena cava obstruction = facial congestion and periorbital oedema, raised non-pulsatile JVP, opening of collateral vessels over the upper chest, upper limb oedema

 

Image result for superior vena cava obstruction collateral

Collateral vessels in SVCO

Recurrent laryngeal nerve palsy = hoarseness, bovine cough

 –Phrenic nerve palsy = raised hemi-diaphragm (more of an x-ray finding

Complications can be due to direct compression by tumour or by adjacent lymph node enlargement.

Metastatic spread: commonly to skin, bone, liver, adrenals, brain =

-bony pain and tenderness

-anaemia or hypercalcaemia due to bone infiltration

-confusion, fits

-focal neurological signs

-proximal myopathy

-peripheral neuropathy

-cerebellar ataxia (inability to coordinate balance, gait etc.)

-Addisons’s disease

Paraneoplastic syndromes:

Endocrine

-Hypercalcemia (PTH related peptide secretion: constipation (or diarrhoea), nausea or vomiting, confusion, coma (Squamous cell tumours)

SIADH (syndrome of inappropriate SIADH → dilutional hyponatraemia): confusion, coma and death if Na gets very low (Small cell tumours)

ACTH secretion– Cushing’s syndrome: central weight gain, easy bruising, moon face, buffalo hump, proximal myopathy, striae (small cell tumours)

Gynaecomastia

Skeletal      

Hypertrophic osteoarthropathy-painful swelling in wrists and ankles (most common with adenocarcinomas and other non-small cell carcinomas)

 

Image result for hypertrophic osteoarthropathy

Irregular periosteal surface of bone due to new periosteal formation

Clubbing (except in small cell lung cancer)

Neuromuscular (rare)

Peripheral neuropathy

-Confusion, fits

Cerebellar ataxia

-Myasthenia syndrome (Lambert-Eaton Syndrome): weakness of muscle groups in the pectoral and pelvic girdle which improves on repeated activity

-Proximal myopathy, polymyositis, dermatomyositis

Renal (extremely rare)

Nephrotic syndrome: proteinuria, hypoalbuminaemia, oedema

Skin

Pruritis

Acanthosis nigricans (rare) (particularly with adenocarcinomas) = jet-black discolouration of the axillary crease

Image result for acanthosis nigricans axilla

Erythoderma– skin reddening

Haematological

Anaemia: pallor (conjunctival), tired, breathless, koilonychia

Thrombocytopenia purpura = red or purple non-blanching spots on skin caused by bleeding underneath skin due to low circulating platelets

Image result for thrombocytopenic purpura

Thrombophlebitis migrans = recurring thrombophlebitis characterised by successive crops of tender nodules in affected blood vessels

Prognosis:

Non-small cell: 50% 2 year survival without spread, 10% with spread

Small cell: median survival 3 months without treatment, 1-1.5 years if treated

References: Cheese & Onion, Rapid Medicine, My med school e-lectures, Cancer Research UK, Radiopaedia.org

 

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