lung tumors
TRANSCRIPT
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common type but has recently been replaced by adenocarcinoma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