1. Tumors of the lung Carcinoma 90-95% Carcinoid 5 %
Mesenchymal and others %

2. Tumors of the lung Etiology directly related to cigarette smoking
- Statistical evidence for positive relationship between tobacco smoking and lung carcinoma.
- 87% lung cancers occur in active smokers
- Risk = Average smokers (x10), heavy smokers (>40/day) (x60)
- Passive smokers also have higher risk

3. Tumors of the lung Etiology directly related to cigarette smoking
- Clinical evidence.
- Changes in bronchial epithelium in habitual smokers (metaplasia, dysplasia, carcinoma in situ, squamous carcinoma)

4. Tumors of the lung Etiology directly related to cigarette smoking
- Experimental evidence.

6. Lung carcinoma - Other Environmental factors:
Radiation, air pollution (radon), asbestos

7. Lung carcinoma Oncogenes associated with lung cancer
Series of genetic abnormalities occurring in a step-wise manner, triggered by a combination of genetic and environmental factors
Oncogenes associated with lung cancer
- cMYC, K-RAS, EGFR, HER-2/Neu
- p53, RB, p16

8. Initiators: Promotors: polycyclic aromatic hydrocarbons
phenol derivatives

9. WHO classification (epithelial tumors)
- Squamous
- Small cell
- Adeno (with variants)
- Large cell
- Adeno-squamous
- Ca with pleomorphic sarcomatous elements
- Carcinoid
- Salivary gland type
- Unclassified

10. Incidence Cancers (except adeno) are centrally located Squamous 25-40%
Small cell %
Large cell %
Increasing incidence of adenoca
- Women smokers
- Type of cigarettes
Cancers (except adeno) are centrally located
Practical aspect:
- Small cell Ca: metastasize, show high initial chemoresponsiveness
- Non-small cell ca: less metastases, less chemoresponsiveness

12. Lung Carcinoma - Morphology (squamous)
- Most are centrally located (except adenocarcinomas), from first to third order bronchi

13. Squamous cell carcinoma:
- Close correlation with smoking history
- Begins as dysplasia - carcinoma in situ - irregular warty growth with elevation and erosion of bronchial mucosa
- fungates into the lumen
- penetrate bronchus and infiltrate along wall
- cauliflower like intraparenchymal mass
- extension to pleura
- spread to lymphnodes (>50% cases)
- distant spread

14. Squamous cell carcinoma:
- Histology:
- Malignant squamous cells with keratinization and intercellular bridges
- Varying degrees of differentiation
- Genetic alterations
- highest frequency of p53 mutations
- this increases with increasing grade
- high expression of EGFR

15. Adenocarcinoma - Most common cancer in women and nonsmokers
- More peripherally located and smaller in size
- Often show mixed pattern (acinar, papillary, bronchiolo-alveolar, solid with mucin
- Grow more slowly when compared to squamous, but metastasize widely

16. Bronchioloalveolar carcinoma
- Almost always peripheral
- Usually appears as multiple nodules with pneumonia like consolidation
- Nodules have mucoid feel
- Microscopic growth pattern is characteristic and resembles butterflies on a fence
- Mucinous and non mucinous subtypes
- Nonmucinous tumors are surgically resectable

17. Bronchioloalveolar carcinoma

18. Aggressive tumors, strong relationship to smoking
Small cell carcinoma
Aggressive tumors, strong relationship to smoking
Central location
Whitish appearance
Small cells
Granular chromatin
High mitotic activity
Nuclear moulding
Dense core neuro- secretory granules

19. Staging of lung cancer:
TNM staging is used for staging cancer based on anatomic extent of tumor (T), lymph node metastases (N), and distant hematogenous metastases (M).
Useful for comparing treatment results from different centers
Adenocarcinoma and squamous cell carcinoma tend to be localized for longer periods.
Small cell carcinoma is particularly responsive to radiation and chemotherapy

20. Clinical Course - Most insidious and aggressive neoplasm
- Cough, weight loss, hemoptysis, chest pain, dyspnoea
- Paraneoplastic syndromes due to hormone like substances
Small cell carcinoma ADH, ACTH,
Squamous cell carcinoma - PTH,
Carcinoid tumors Serotonin, Bradykinin
Others Calcitonin, Gonadotropins,
Eaton-Lambert syndrome (Ca channel antibodies)
Peripheral neuropathies, clubbing

21. Clinical Course Local tumor effects:
Pneumonia, abscess, collapse Airway obstruction
Lipid pneumonia Secondary to obstruction
Pleural effusion Tumor spread
Hoarseness RLN invasion
Dysphagia Esophageal invasion
Diaphragm paralysis Phrenic nerve invasion
Rib destruction Chest wall invasion
SVC syndrome SVC compression
Horner syndrome Symp ganglia invasion
Pericarditis / tamponade Pericardial invasion

22. Metastatic tumors
Usually multiple “cannon-ball” lesions more in the periphery
Variety of other patterns may also be seen

23. Malignant mesothelioma:
- From parietal / visceral pleura
- Related to asbestos exposure
- Diffuse involvement of pleural space with effusion and invasion of thoracic structures
- Microscopically, epithelioid and sarcomatoid subtypes