Bronchogenic carcinoma

Published on 02/04/2015 by admin

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Last modified 22/04/2025

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104 Bronchogenic carcinoma

Instruction

Examine this patient’s chest.

Salient features

History

• Symptoms related to primary tumour: cough, dyspnoea, haemoptysis, postobstructive pneumonia)

• Symptoms related to mediastinal spread:

• Hoarseness with left-sided lesions (caused by recurrent laryngeal nerve palsy)
• Obstructive of the superior vena cava with right-sided tumours or associated lymphadenopathy
• Elevation of the hemidiaphragm from phrenic nerve paralysis
• Dysphagia from oesophageal obstruction and pericardial tamponade.

• Symptoms related to metastases:

• Sites include liver, brain, pleural cavity, bone, adrenal glands, contralateral lungs and skin
• Initial presentation with symptoms from a metastatic focus is particularly common with adenocarcinoma.

• Paraneoplastic syndrome:

• Pain or arm in legs caused by hypertrophic osteoarthropathy
• Symptoms of hypercalcaemia caused by squamous cell carcinoma
• Neurological syndromes.

• Systemic effects: anorexia, weight loss, weakness and profound fatigue.

• History of smoking

Examination

Patient 1

• Clubbing and tar staining the fingers

• Dull percussion note at the apex with absent breath sounds.

Look for Horner syndrome and wasting of the small muscles of the hand.

Patient 2

• Signs of pleural effusion on one side.

Patient 3

• Signs of unilateral collapse or consolidation of the upper lobe on one side.

Note: If you suspect bronchogenic carcinoma, always look for clubbing, tar staining, cervical lymph nodes and radiation marks, and comment on cachexia.

Diagnosis

This patient with marked clubbing and large pleural effusion (lesion) probably has bronchogenic carcinoma (aetiology) and is very short of breath because of the large effusion (functional status).

Questions

How may patients with bronchogenic carcinoma present?

• Cough (in 80%), haemoptysis (70%) and dyspnoea (60%); loss of weight, anorexia

• Skeletal manifestations: clubbing (in 30%)

• Local pressure effects: recurrent laryngeal palsy, superior vena caval obstruction, Horner syndrome

• Endocrine manifestations (12% of the tumours)—in particular small cell tumours—present with syndrome of inappropriate antidiuretic hormone (SIADH), hypercalcaemia, adrenocorticotrophic hormone (ACTH) secretion or gynaecomastia. SIADH does not usually cause symptoms. When Cushing syndrome occurs, the manifestations are primarily metabolic (hypokalaemic alkalosis)

• Neurological manifestations: Eaton–Lambert syndrome, cerebellar degeneration, polyneuropathy, dementia, proximal myopathy, encephalomyelitis, subacute sensory neuropathy, limbic encephalitis, opsoclonus, myoclonus

• Cardiovascular: thrombophlebitis migrans, atrial fibrillation, pericarditis, non-bacterial thrombotic endocarditis

• Cutaneous manifestations: dermatomyositis, acanthosis nigricans, herpes zoster

• Anaemia, disseminated intravascular coagulation, thrombotic thrombocytopenic purpura. Hypercoagulatopathy in the form of venous thromboembolism is seen especially with adenocarcinoma

• Membranous glomerulonephritis.

How would you investigate this patient?

• Sputum cytology: high yield for endobronchial tumours such as squamous cell and small cell carcinoma) but the yield is poor for adenocarcinoma

• Chest radiography (Fig. 104.1)

• Pleural fluid cytology

• Bronchoscopy gives a high yield in excess of 90%, particularly when the tumour is viewed endobronchially. For tumours that are not visualized, the yield for washing and brushing is about 75% in central lesions and 55% in peripheral lesions. The yield in small cell and squamous cell carcinomas is higher than adenocarcinomas

• CT scan of the chest and upper abdomen (to image the liver and adrenals)

• Bone scan for metastases (helpful in staging)

• PET scanning is highly sensitive and specific for mediastinal staging

• Pulmonary function tests (most surgeons aim for a FEV1 of about 1000 ml after planned resection), a DLCO (carbon monoxide diffusing capacity of the lung) <60% predicted is associated with a mortality rate as high as 25% as a result of respiratory complications.

image

Fig. 104.1 Right upper lobe collapse with peripheral concavity and central convexity (arrows) caused by an underlying bronchogenic carcinoma resulting in a reverse S shape (Golden’s ‘S’ sign).

(With permission from Adam et al. 2008.)

Advanced-level questions

What is the aim of staging?

The main aim of staging is to identify candidates for surgical resection, since this approach offers the highest potential cure for lung cancer. The staging assessment covers three major issues: distant metastases, the state of chest and mediastinum and the condition of the patient.

What is the role of surgery in lung carcinoma?

Surgery is beneficial in peripheral non-small cell carcinoma. Its role is limited in small cell carcinoma as >90% would have metastasized by the time of diagnosis. Surgery should include resection (pneumonectomy or lobectomy) and mediastinal node mapping. Complete lymph node dissection should be performed if the tumour is resectable and mediastinal nodes are involved.

Which tumours respond well to chemotherapy?

Small cell carcinoma: cyclophosphamide, doxorubicin, cisplatin, etoposide and vincristine are some of the drugs used. The combination of etoposide and cisplatin appears to have the best therapeutic index of any regimen. A meta-analysis on the role of chemotherapy in non-small cell lung cancers suggested that the benefits are small.

What are the drugs used in non-small-cell lung cancer?

• Old agents: cisplatin, carboplatin, etopside, vinblastine, vindesine

• Newer agents: docetaxel, paclitaxel, irinotacen, vinorelbine, gemcitabine

• Vascular endothelial growth factor (VEGF) inhibitors: bevacizumab

• Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (e.g. gefitinib, erlotinib. cetuximab): most effective in women, patients who have never smoked, patients with pulmonary adenocarcinomas and patients of Asian origin.

The EGFR family of surface-receptor tyrosine kinases contains four members, which can form homodimers or heterodimers after ligand binding. Dimerization results in the activation of tyrosine kinases, which is followed by stimulation of three major signalling pathways, eventually leading to the activation of five of the six hallmarks of cancer: angiogenesis, resistance to antigrowth signals, invasion and metastasis, self-sufficiency in growth signals, and evasion of apoptosis (the sixth hallmark being limitless replication). The vast majority of EGFR mutations are either a deletion of a conserved sequence in exon 19 or a single point mutation in exon 21 (L858R).

What are the indications for radiotherapy?

Radiotherapy is administered for palliation in the following circumstances:

• Pain: either local or metastatic

• Breathlessness caused by bronchial obstruction

• Dysphagia

• Haemoptysis

• Superior venal caval obstruction

• Pancoast’s tumour

• Before and after operation in selected patients

• Cerebral metastases.

What are the contraindications for surgery?

• Metastatic carcinoma

• FEV1 <1500 ml

• Transfer factor <50%

• Severe pulmonary hypertension

• Uncontrolled major cardiac arrhythmias

• Carbon dioxide retention

• Myocardial infarction in the past 3 months.

Is the progression of cancer associated with genetic change?

Yes: it is accompanied by a mutation in the p53 gene and loss of a portion of the short arm of chromosome 3 in small cell cancer; the functional significance of this is not clear.

What is the prognosis?

Survival after diagnosis for small cell carcinoma is 3 months if untreated and 18 months with treatment.

Survival after diagnosis for non-small cell carcinoma is 50% if there are no metastases and 10% with metastasis.

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