10. Respiratory tract:neoplastic disease

Question 1

Lung tumours

Answer 1

Benign and malignant tumors may arise in lung
Vast majority (90% to 95%) are carcinomas (arising from lining epithelium)
About 5% are bronchial carcinoids (neuroendocrine)
2% to 5% are mesenchymal and other miscellaneous neoplasms including sarcomas and lymphomas

Question 2

Lung carcinomas

Answer 2

2nd most common cancer in UK
Incidence increasing in females, decreasing in males
Age 40-70 years
Male > female
5 year survival 8% (men), 9% (women)

Question 3

Risk factors

Answer 3

Smoking
Industrial hazards
High dose ionising radiation
Uranium
Asbestos
Radon
Silica 
Diesel exhaust/air pollution
Family history
Immunodeficiency

Question 4

Smoking

Answer 4

Statistical evidence
87% of lung carcinoma in active smokers/recently stopped smoking
10 fold ↑ risk for average smokers, 60 fold ↑ risk for heavy smokers (>40/day for several yrs)
3000 non smokers die of lung ca/year – passive smoking
Cigar/pipe - ↑ risk, but less so than cigarettes
Clinical evidence
Linear correlation between exposure to cigarette smoke and epithelial changes (metaplasia, dysplasia, CIS, invasive carcinoma)
Also associated with carcinoma of the mouth, pharynx, larynx, oesophagus, pancreas, cervix, kidney and bladder

Question 5

Clinical details

Answer 5

Presenting complaint
Cough (75%)
Weight loss (40%)
Chest pain (40%)
Dyspnoea (20%)

May present with symptoms of metastases
Local extension of tumour within pleural cavity, to pericardium
Spread to tracheal, bronchial and mediastinal nodes found in most cases; nodal involvement average >50%
Most common distant spread adrenals (>50%), liver (30-50%), brain (20%), bone (20%)

Question 6

Local effects of lung tumour spread

Answer 6

Pneumonia, abscess, lobar collapse = Obstruction of airway
Pleural effusion = Spread into pleura
Hoarseness = Recurrent laryngeal nerve invasion
Dysphagia = Oesophageal invasion
Diaphragm paralysis = Phrenic nerve invasion
Rib destruction = Chest wall invasion
SVC syndrome = SVC compression by tumour
Horner syndrome = Sympathetic ganglia invasion
Pericarditis, tamponade = Pericardial involvement

Question 7

Paraneoplastic syndromes

Answer 7

Ectopic hormone secretion by tumour
Incidence 1-10% of all lung cancer patients
Hormones involved include:
Antidiuretic hormone (ADH) – hyponatraemia
Adrenocorticotrophic hormone (ACTH) – Cushing syndrome
Parathormone, parathyroid hormone-related peptide, prostaglandin E, cytokines – hypercalcaemia
Calcitonin – hypocalcaemia
Gonadotropins – gynaecomastia
Serotonin and bradykinin – carcinoid syndrome

Question 8

Lung carcinoma

Answer 8

Staging – TNM staging

Treatment –
Surgical
Chemotherapy – targeted therapy for EGFR mutation
Radiotherapy

Prognosis:
15% overall 5-year survival
(48% for cases detected when still localised) adenocarcinoma, SCC – slightly better prognosis, tend to remain localised longer

Question 9

Lung Carcinoma – Staging - TNM

Answer 9

T’ - Primary tumour size/degree of invasion?

‘N’ – Lymph nodes positive or not ?

‘M’ – Distant metastases or not ?

Question 10

Size cut-offs for T1, T2 and T3 tumours

Answer 10

> 7cm T3

Question 11

Classification

Answer 11

Small cell carcinoma (20-25%)

Non-small cell carcinoma
Squamous cell carcinoma (25-40%)
Adenocarcinoma (25-40%)
Large cell carcinoma (10-15%)

Combined carcinoma

Question 12

Small cell carcinoma (1)

Answer 12

Strong relationship to smoking – 1% occur in non smokers
Occur in major bronchi and at periphery
Rapidly invade bronchial wall and parenchyma; early lymphatic and blood-borne spread
Therefore mostly incurable by surgery
Most responsive to chemotherapy – but worst prognosis as relapses early

HISTOPATHOLOGY: small, tightly packed, darkly stained ovoid tumour cells (resemble oats – also termed oat cell carcinoma)

Question 13

Small cell carcinoma (2)

Answer 13

Cells with little cytoplasm
Finely granular nuclear chromatin (“salt + pepper”)
Absent or inconspicuous nucleoli
Can be pure or combined (with any other non-small cell type)

Question 14

Other histological features

Answer 14

Nuclear molding
Crush artifact
Necrosis
High mitotic index

Question 15

Squamous cell carcinoma (1)

Answer 15

Most commonly affects men
Closely correlated with smoking history
Arises close to hilum, usually in area of squamous metaplasia (due to cigarette smoke)

HISTOPATHOLOGY: well differentiatied resembles stratified squamous epithelium; characterised by keratin formation and/or intercellular bridges

Question 16

Squamous cell carcinoma (2)

Answer 16

Usually arise centrally from the bronchi
Keratinisation and/or intercellular bridges
2/3 central (segmental bronchi)
90% of cases are smokers

Question 17

Adenocarcinoma (1)

Answer 17

Most common type in women and non-smokers (but >75% found in smokers)
Tend to be peripherally located
Grow more slowly than SCC but metastasize early and widely
Sometimes associated with scarring e.g. healed TB

HISTOPATHOLOGY: well differentiated have obvious glandular elements; 80% contain mucin

Question 18

Adenocarcinoma (2)

Answer 18

2/3 peripheral
Grow more slowly than squamous cell carcinomas but tend to metastasise widely and earlier
Peripheral adenocarcinomas are sometimes associated with areas of scarring

Question 19

Large cell carcinoma

Answer 19

Undifferentiated malignant epithelial tumour
Undifferentiated SCC and adenocarcinoma with no discernible features by light microscopy
HISTOPATHOLOGY: large, anaplastic epithelial cells growing in islands and sheets
Neuroendocrine variant – highly malignant; nests and islands of tumour cells with granular cytoplasm, central necrosis, peripheral palisading

Question 20

Lung metastases

Answer 20

Most common site of metastatic neoplasms
Arrive by blood, lymphatics or direct continuity
Usually multiple discrete nodules (cannonball lesions) scattered thoughout all lobes
Peripheral lesions
Common primary sites- bowel, prostate, breast, kidney

Question 21

Pleural tumours

Answer 21

Secondary metastatic involvement more common than primary tumour
Most frequently lung or breast
Serous/serosanguinous effusion often present containing neoplastic cells
Primary tumour
Malignant mesothelioma

Question 22

Malignant mesothelioma (1)

Answer 22

Increased incidence in people with exposure to asbestos
Lifetime risk in heavily exposed individuals as high as 7-10%
Latent period of 25-45 years
No increased risk in asbestos workers who smoke
Diffuse lesion that spreads widely in the pleural space
Associated with extensive pleural effusion and direct invasion of thoracic structures

Question 23

Malignant mesothelioma (2)

Answer 23

Plaques resulting from asbestos exposure can be found on the pleural surfaces
Histology - asbestos bodies are found in increased numbers in the lungs of patients with mesothelioma
Affected lung is ensheathed by a thick layer of soft, gelatinous, greyish pink tumour tissue

Question 24

Malignant mesothelioma (3)

Answer 24

Presents with chest pain, dyspnoea, pleural effusions
50% die within 12 months of diagnosis
Invades lung directly
Often spread to hilar LN, and eventually to liver and other organs
Treatment:
Extra-pleural pneumonectomy, chemo, radiotherapy
Doesn’t often improve prognosis
Mesothelioma also arises in peritoneum, pericardium, genital tract