Tumors of the lung Carcinoma 90-95% Carcinoid 5 % Mesenchymal and others 2-5 %

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

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)

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

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

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

Initiators: Promotors: polycyclic aromatic hydrocarbons phenol derivatives

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

Incidence Cancers (except adeno) are centrally located Squamous 25-40% Small cell 20-25% Large cell 10-15% 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

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

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

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

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

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

Bronchioloalveolar carcinoma

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

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

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

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

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

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