Lung and Mediastinal Tumours

Dr. Manu Mohan. K

Associate Professor

Pulmonary Medicine

Epidemiology

Most common form of malignant diseases

40,000 new patients per year8% male deaths and 4% of all

female deathsMen > women, middle age

Etiological factors

Tobacco smokingCigarette smokers are 8-20 times more likely to

develop lung cancer than life long non smokers.Squamous and small cell carcinoma have clear

association with smoking.Adenocarcinoma is commonest histological type in

a non smoker

Atmospheric pollution

Controversial

Radon - radiation

Occupational factors

Asbestos – mining, processing, usage.

Radioactivity – metal ore mining, uranium mining.

Nickel – refining.Chromium salt – extraction,

production, usage.Arsenic – metal refining, chemical

industry, insecticides.

Pulmonary scarring

Localised areas of pulmonary scarringDiffuse pulmonary fibrosisCryptogenic fibrosing alveolitis is

associated with adenocarcinoma Tuberculosis – scar carcinoma,

adenocarcinomaBronchioloalveolar carcinoma also occur

in areas of scarring

Histological classification

1. Squamous cell carcinoma (epidermoid carcinoma)

2. Small cell carcinoma

a. oat cell carcinoma

b. intermediate cell type

c. combined oat cell carcinoma

3. Adenocarcinoma

a. acinar

b. papillary adenocarcinoma

c. bronchioloalveolar

d. solid carcinoma with mucous

4. Large cell carcinoma

5. Adenosquamous carcinoma

6. Carcinoid tumours

7. Bronchial gland carcinoma

a. adenoid cystic carcinoma

b. mucoepidermoid carcinoma

c. others

Growth factors

Polypeptides that take part in the control of cell differentiation and proliferation

Bombesin/gastrin releasing peptide – growth factor for small cell carcinoma

Non small cell carcinoma – few growth factors are recognized, EGF, TGF

Genetic abnormalities

Loss of short arm of chromosome in small cell carcinoma (p14, p23)

CDKN2 gene on chromosome 9 – Non small cell lung carcinoma

Oncogenes

myc genes – small cell lung carcinoma

Kras – adenocarcinoma

Tumour markers

Substances produced by tumour cells that are released in to blood stream.

Neuron specific enolase, creatinine phophokinase BB, CEA

Modes of presentation

Worsening of preexisting respiratory state.

No symptoms, detected by the chance of finding an opacity.

Nonspecific symptoms of malignancy like malaise, anorexia, and weight loss

Metastatic disease

Central tumours

Cough – most common symptomNew cough that persists longer than 2 weeks

in a patient of 40 years who is a smoker.Hemoptysis – usually streakyBreathlessness – due to central airway

narrowing, partial or total collapse of a distal segment

Chest pain – deep chest discomfort, due to peribronchial and perivascular nerve involvement.

Peripheral tumours

Cough and hemoptyisBronchorrhoeaDyspnoeaChest pain

Distant spread

Skeletal metastasis – bone pain, pathological fractures

Cerebral metastasis – progressive neurological symptoms

Clinical features

Frequently no abnormal findings

HoarsenessBovine coughClubbingHPOA

Lymphatic involvement – scalene and supraclavicular

Axillary lymph nodes due to chest invasion

Stridor, wheezes

Atelectasis Pleural effusionSVC obstructionDiaphragm palsyEnlarged liverRaised intracranial pressureDysphagia

Investigations

Chest radiographyNearly always abnormal

Collapse Pleural effusionElevated hemi diaphragmWidening of mediastinumLymphangitis carcinomatosaPneumonic shadow –

bronchioloalveolar carcinomaPancoast tumour

Solitary pulmonary nodule (SPN)

Opacity of less than 3 cm without surrounding atelectasis and or adenopathy.

Doubling timeCalcification

Solitary pulmonary nodule

Sputum cytology – more yield in central tumours

60-70% positive yield in experienced hands

Single sample – 40%4 samples – 80%

Bronchoscopy – most useful for central tumours

Tumours beyond bronchoscopic view – Transbronchial needle biopsy, blind brushing and washing

Other investigations

Percutaneous needle biopsyAspiration of subcutaneous

swellingPleural fluid studyThoracoscopic lung biopsyMediastinoscopy Thoracotomy

StagingNon small cell carcinoma

TNM stagingPrimary tumour (T)Tx, T0, T1s, T1, T2, T3, T4Nodal involvement (N)N0, N1, N2, N3.Distant metastasis (M)M0, M1

Staging

Small cell lung carcinomaLimited Extensive

Treatment

Non small cell lung carcinoma Surgery – best result, but only a small minority Types of surgery Pneumonectomy Lobectomy VATS – segmentectomy 5 year survival rate overall 35%

Radiotherapy Stage I&II – inoperable due to medical

contraindications Indications Hemoptysis, pain, cough, dyspnoea

due to large bronchus obstruction, mediastinal compression, symptoms due to intracranial metastasis, symptoms due to spinal cord compression.

Endobronchial treatment

Laser therapy Endobronchial radiotherapy Photodynamic therapy

Chemotherapy

Poor response to chemotherapeutic agents Combined modalities

Small cell carcinoma

At presentation 70% have extensive disease

ChemotherapyMore sensitive to chemotherapyCombined therapy preferred than

monotherapy

Radiotherapy Primary tumour controlProphylatic cranial irradiationSurgery

Paraneoplastic syndrome

Non metastatic metabolic/neuromuscular manifestations

Hypercalcemia SIADH Ectopic ACTH HPOA

Gynaecomastia – large cell and adeno carcinoma

Eaton-Lambert syndrome, polymyositis/dermatomyositis

Peripheral neuropathy Cerebellar ataxia

Superior venacava obstruction

Small cell carcinoma Diagnosis – swelling of face and upper

torso and distension of veins across the chest, upper arms and neck.

Treatment – chemotherapy, radiotherapy and stenting

Superior sulcus tumour

Pancoast Pain in lower part of shoulder and

inner aspect of the arm (C8, T1 and T2)

Sympathetic ganglion involvement – stellate

Diagnosis Treatment - radiotherapy and

surgery

Prevention

Primary prevention

Stop smoking

Mediastinum lies centrally within the chest and spans the region vertically from the thoracic inlet to the diaphragmatic hiatus, transversally between the parietal pleura, and coronally between the sternum and vertebral column.

Mediastinal Compartments

3 compartments

Anterior compartment

Middle compartment

Posterior compartment

Symptoms and Mechanisms

Symptoms Mechanisms

cough Airway narrowing, compression

Chest pain Chest wall invasion, neural invasion

Dyspnoea Airway compromise, pericardial tamponade, pleural effusions, pulmonary stenosis, heart failure.

Hemoptysis Bronchogenic carcinoma, airway invasion, pulmonary stenosis, heart failure

Dysphagia Oesophageal narrowing/obstruction, oesophageal motor dysfunction

Hoarseness Vocal cord paralysis

Facial swelling Superior vena cava syndrome

Incidence

Adults

65% in Anterosuperior, 10% in the middle and 25% in the posterior compartments

Children

28% Anterosuperior, 10% in middle, 62% in the posterior compartment

Investigations

• Noninvasive diagnostic procedures• Computed tomography• Magnetic resonance imaging• Ultrasonography• Radio nuclides

Biochemical Markers CEA AFB, HCG – nonseminomatous germ cell

tumour, Teratoma, Carcinoma Catecholamines,vanillylmandelic acid,

homovanillic acid – Pheochromocytoma Nor epinephrine, epinephrine –

paraganglioma,ganglioneuroma, neuroblatoma

Invasive biopsy procedures

FNAB

Surgical procedures

Lesions masquerading as mediastinal tumours

• Substernal Goiter• Cystic Hygroma• Lesions originating from thoracic

skeleton• Vascular lesions• Oesophageal lesions• Pulmonary lesions• Sub diaphragmatic Lesions

Paraneoplastic syndromes associated with Thymoma

Well establishedMyasthenia gravisPure red cell aplasiaAcquired

hypogammaglobulinemiaNon Thymic cancers

Less well establishedPancytopeniaLambert-EatonPeripheral neuropathiesCNS changesMultiple endocrine defectsMultiple rheumatologic disordersNephrotic syndrome

Thymoma is the most common primary neoplasm of the mediastinum

15% of Thymic lesionsEqual frequency in male and female40-60 years75% in anterior mediastinumMore than 90% are visible on chest

radiograph

Surgical resectionRadiotherapyUnresectable, recurrent or

metastatic Thymoma- chemotherapy

Tumours of lymph nodes

Lymphomas 10-14% of mediastinal tumoursRare in posterior mediastinum Hodgkin’s and Non Hodgkin’s20-30% asymptomatic60-70% symptoms of local invasion30-35% systemic symptoms

Non-Hodgkin’s lymphoma5% with mediastinal involvementLarge irregular anterior and

superior mediastinal involvementRadiation therapy effective in low

grade lymphomachemotherapy

Germ cell tumours

Benign and malignant

Benign germ cell tumours (Teratoma)

Constitute 70% of the lesions in children and 60% in adults.

Contain multiple tissues that are foreign to the part of the body in which they develop.

Symptomatic only when infected

Malignant germ cell tumours

Malignant mediastinal teratomaMediastinal seminomaNonseminomatous tumours-

embryonal carcinoma, choriocarcinoma, endodermal sinus tumours, teratocarcinoma

Chemotherapy and radiotherapy, surgery

Middle mediastinal tumours

Bronchogenic cystsMediastinal cysts form 20% of mediastinal tumours

60% of mediastinal cysts are bronchogenic cyst

Oesophageal cysts Neuroenteric cystsMesothelial cysts

Pericardial or pleuropericardial cysts

Thoracic duct cyst

• Neurogenic tumours• Most common malignancy in

children• In children 50% malignant,

adults 10%• Dumbbell tumours – intraspinal

extension• CT, MRI, myelography

Posterior mediastinal tumours

Tumours of nerve sheath originBenign – neurilemoma or

neurofibromaMalignant tumours-incidence

of malignancy more in von Recklinghausen’s disease

Poor prognosis

Tumours of autonomic nervous systemNeuroblatoma,

ganglioneuroblastoma rare in adults

Endocrine tumours

Mediastinal pheochromocytoma

Parathyroid adenoma