LUNG TUMORS

LUNG TUMORS

Primary :• 95 % are Bronchogenic Carcinoma– Extremely common – M:F = 2:1 , Age 55-65

• 5% are Bronchial carcinoids Mesenchymal malignancies Lymphomas Benign lesions: hamartomaSecondary : very common

Bronchogenic Carcinoma:

• Commonest cause of cancer related deaths in males, and in the US in females as well

• The rate of increase is declining in males but is accelerating in females

• Majority are related to smoking• Bad prognosis ( 5 year survival for all stages of

lung cancer combined < 15%)• If localized to lung 5 yr survival is 45%

Types of Lung carcinoma :

• SMALL CELL LUNG CANCER (SCLC)– Small Cell Carcinoma

• NON SMALL CELL LUNG CANCER : NSCLC– Squamous Cell Carcinoma–Adenocarcinoma– Large Cell Carcinoma

• Note : Combined patterns are possible

- Squamous cell carcinoma was the most

common type but has recently been replaced by adenocarcinoma

- Adenocarcinoma most common type in females, nonsmokers and patients < 45 years

• Division is for therapeutic purposes• Virtually all SCLC have metastasized by time of

diagnosis →→ treated by chemotherapy +/- radiotherapy

• NSCLC better treated by surgery• Genetic differences: SCLC : RB gene mutation NSCLC: p16/CDKN2A gene inactivation KRAS & EGFR oncogene mutation

Etiology

1- Cigarette smoking – risk –Contains numerous carcinogens– Up to 90% squamous & small cell CA occur in smokers– Correlation between smoking in pack years & lung CA : 60X increased risk in heavy

habitual smokers– Passive smoking : 2X– Effect of carcinogen is genetically conditioned

2 - Genetic Factors :

• Stepwise accumulation of genetic mutations triggered by carcinogens

• Earliest is inactivation of suppressor gene on chromosome 3P

• Later mutations in P53 & K- RAS …etc :– Activating mutations in EGFR & K-RAS in adenocarcinoma– RB mutation in Small Cell Carcinoma– P 16/ CDKN2A inactivation in NSCLC

3- Environmental Hazards :

• Asbestos workers• Uranium workers• Exposure to radiation• Nickel , arsenic , chromate….etc

4- Scarring in lung tissue ( Scar Cancer ) usually adenocarcinoma

Diagnostic techniques for lung cancer :

1- Chest X ray, CT, …..etc 2- Sputum Cytology & bronchial wash 3- Bronchial biopsy : Biopsy taken by bronchoscope 4- Transbronchial biopsy : forceps down bronchoscope into lung parenchyma to take a biopsy. 5- Transcutaneous needle biopsy 6 -Open lung biopsy

A- Squamous cell CA B- Small Cell CA

Gross appearance of most types :

Central• Thickening of mucosa• Later may show irregular whitish warty

lesion ulceration • Infiltration of wall of bronchus into lung• Hemorrhage, necrosis & cavitation may be

seenPeripheral:• Consolidated rounded lesion

Central Cancer

Peripheral Cancer

1- SQUAMOUS CELL CA :

• Male> female, > 90% in smokers • Usually central location, Warty ± cavitation• May present with HYPERCALCEMIA• Precursor Lesion:

– Squamous metaplasia Dysplasia Carcinoma in Situ Squamous cell CA

• Histology :Various degrees of squamous differentiation ± Keratin formation

• Prognosis better than Small Cell CA

Squamous metaplasia & Carcinoma in situ

2- ADENOCARCINOMA :

• Commonest in females• Least associated with smoking • Usually peripheral but may be central• Growth is slower than squamous but widely metastasize• Types include : A- Usual bronchial derived ( 80%) ±mucin. May be:– Acinar– Papillary– Solid

• B- Bronchioloalveolar CA :

• Multifocal diffuse or localized nodule .• Peripheral location• May present as pneumonic consolidation• Growth along alveolar walls without

destruction of walls (non-invasive)• Prognosis of better than usual adenocarcinoma.

Bronchioalveolar Carcinoma

Precursor Lesions in Adenocarcinoma:

• ? Presence of Bronchioalveolar Alveolar Stem Cells (BASC) expansion after lung injury

• Atypical Adenomatous Hyperplasia (AAH) → Bronchioalveolar CA →

Adenocarcinoma

• AAH has same 3P deletion & K-RAS mutation similar to CA

3- LARGE CELL ANAPLASTIC CARCINOMA :

• Poorly differentiated tumors • Difficult to type, may need special

immunostains.• Incidence is about ( 10-15 % )• Probably poorly differentiated Squamous Cell

CA or Adenocarcinoma• Prognosis is poor

4- SMALL CELL CARCINOMA (SCLC)

• Male > Female , >90% in smokers• Arise from neuroendocrine cells• Central mass • Most aggressive,necrosis, metastasize early • Most frequent type with ectopic hormones• Cytology: Crush artefact, nuclear molding• Histology : Small blue cells (Oat Cell CA) mitosis+

+,necrosis++

A- Squamous cell CA B- Small Cell CA

Types of Bronchial Carcinoma

Spread of lung cancer :

1- Local extensionpleura , pericardium & mediastinum ,nerves & vessels

2- Lymph node metastases regional L.N. ,bronchial, tracheal and mediastinal

3-Distant metastases : Adrenal (> 50% ) , Liver , Brain , bone …

Staging of Lung CA

• BASED ON TNM STAGING SYSTEM :

• Stage I = T1 N0 M0 (tumor <3cm.)• Stage II = T2 N1 M0 ( tumor 3cm.)• Stage III = T3 N1 M0 ( tumor involving chest

wall, mediastinum, contralateral nodes….etc.)

• Stage IV = Any T, any N, M1

Local & regional invasion :

i- Lymphatic : carina, mediastinum & neck- Mediastinal invasion – Recurrent laryngeal n. on left vocal cord

paralysis– Phrenic nerve diaphragmatic paralysis– Esophagus bronchoesophageal fistula– Cardiac & pericardial invasion– Chest wall invasion Pain & pleural effusion

Late invasion of upper lobe tumors :• Right upper lobe tumors or LN’s compress SVC

Superior Vena Cava Syndrome

• Apical tumors ‘Pancoast’tumor :

– Brachial plexus Pain in distribution of ulnar nerve– Destruction of 1st.&2nd.rib ± vertebrae – Sympathetic chain invasionHorner’s Syndrome (ipsilateral enophthalmus,ptosis,miosis &anhydrosis )

Extrathoracic Metastases : adrenals no symptoms bone pain , fracture,Ca & alkaline phosphatase brain headache, convulsions …. etc liver incidental or hepatomegaly, ascitis…etc.

Paraneoplastic Syndrome :

Present in 10% of tumors, most in SCLC• Ectopic hormone production :– ADH , ACTH, Gonadotrophic H….in SCLC– PTH relared peptide→↑ Calcium in Squamous cell

CA

• Migratory thrombophlebitis, DIC in AdenoCA• Digital clubbing,hypertrophic osteoarthropathy• Neuromuscular disorders …etc in SCLC

Carcinoid tumor (neuroendocrine cancer grade I)

• Younger age than CA , 5% of lung tumors• Arise from neuroendocrine cells • Most arise in bronchial wall, fill lumen or extend into lung• Histology: Uniform cells , absent mitoses , arranged in

nests, cords .• Atypical Carcinoid : Show mitoses , necrosis, atypia

Symptoms :

• Obstruction & atelectasis • Infection • Most cases are hormonally inactive but few produce the Carcinoid syndrome • Surgery curative in most cases • About 30 % may metastasize to lymph nodes ± distant metastases

Carcinoid tumor

Metastatic tumors in lung

• All types of carcinomas or sarcomas can metastasize to the lung

• Reach lung by lymphatic or hematogenous route & may show :– Multiple discrete nodules , (Cannon Ball )– Single nodule– Diffuse lymphatic dissemination called

Lymphangitis Carcinomatosa • Pleural effusion is common in metastatic tumors

Tumor- like lesions of the lung :

Lung Hamartoma : • Consists of cartilage,& clefts lined by respiratory epithelium surrounded by connective tissue• Usually peripheral , & incidental ( Coin Lesion )• May simulate tumor radiologically

PLEURAL EFFUSION

• Pleural effusion is a common manifestation of both primary and secondary pleural diseases. Normally, no more than 15 mL of serous, relatively acellular, clear fluid lubricates the pleural surface.

• Pleural Effusion : Accumulation of fluid– Transudate – CHF, Liver failure ,Renal failure– Exudate - Pneumonias – Hemorrhagic- Cancer ,TB, Infarcts

•

• Increased accumulation of pleural fluid occurs in the following settings: • Increased hydrostatic pressure, as in congestive heart failure • Increased vascular permeability, as in pneumonia • Decreased osmotic pressure, as in nephrotic syndrome • Increased intrapleural negative pressure, as in atelectasis • Decreased lymphatic drainage, as in mediastinal carcinomatosis

PLEURA

• Hemothorax : Blood in pleural cavity– Trauma – Rupture of dissecting aneurysm

• Pyothorax/Empyema : Pus in pleural cavity

• Chylothorax : – Accumulation of milky, lipid rich fluid due to lymphatic

obstruction, usually be tumor• Pneumothorax :

– Traumatic – Penetrating injury– Spontaneous : TB,emphysema , Asthma

• Tension Pneumothorax :– Medical emergency with air entering under pressure

Atelectasis

• Clinical Picture :

Chest pain– Ipsilateral shoulder pain – diaphragm–Non-productive cough

• Compression Atelectasis

PLEURAMalignant Mesothelioma :

• Rare tumors of mesothelial cells • Exposure to asbestos in >50%• Long latent period• Not related to smoking

• Pathogenesis :– Inactivation of several tumor suppressor genes– Simian virus 40 viral DNA in 60-80% cases

inactivates p53 & RB

Morphology :

• Starts as pleural fibrosis & plaque• Later firm yellowish white tumor around the pleura• Microscopically : mixed pattern– Epithelial– Sarcomatoid– Biphasic

• Prognosis : POOR

Tumors in Upper Respiratory Tract :

• Nasopharyngeal Carcinoma :– EBV related– Squamous cell & Undifferentiated carcinoma – Numerous lymphocytes(Lymphoepithelioma)

• Laryngeal Tumors :– Benign : Polyps & Papillomas– Malignant : Carcinoma

Laryngeal Carcinoma :

• Squamous cell CA• Middle age , M>F• Etiology : Smoking & Alcohol• Mainly on vocal cords → hoarseness of

voice • Carcinoma in situ → Invasive squamous cell carcinoma → Lymph nodes & neck• May be cured if early