1. Clinical Impression: BRONCHOGENIC CARCINOMA

3. Small cell lung carcinoma 20 % of lung cancer Anaplastic and highly malignant Displays neuroendocrine properties RB mutation in 90% and p16 abnormalities in 10% but never have KRAS and EGFR mutation Histopathologic image of small cell carcinoma of the lung. CT- guided core needle biopsy. H & E stain.

4. Non-small cell lung carcinoma 75% of lung cancer Grows and spreads more slowly than small cell Ca Includes adenocarcinoma, squamous, large cell carcinoma, bronchioloalveolar carcinoma, and mixed version. RB mutation 20%, p16 changes 50%, KRAS mutation 30%, and EGFR 10% Bronchiolo-alveolar carcinoma of the lung with mucin production. Hematoxylin and eosin stain

7. Cigarette smoking/ Tobacco exposure (~90%) Occupational associations: asbestos, uranium( in miners), arsenical fumes, nickel,radon gas. Genetic factors Chronic lung disease: TB & COPD Other factors include air pollutions, ionizing radiation.

8. Initiated by activation of dominant oncogenes and inactivation of tumor-suppressor gene or recessive oncogenes cancer stem cell A small subpopulation of cells with a tumor are responsible for the full malignant behavior of the tumor which are called cancer stem cell this will be important to identify since successful treatment of the tumor will require the eradication of this stem cell component.

9. changes in all myc family members Small Cell Lung CA occasional mutations in BRAF and PIK3CA or activation of the PIK3CA/AKT/mTor pathway amplification, rearrangement, and/or loss of transcriptional control of myc family oncogenes (c-, N-, and L-myc; changes in c-myc Non-Small Cell Lung CA Point mutation in the coding region of RAS family of oncogene (KRAS) Mutation of tyrosine kinase domain of the EGFR Adenocarcinoma

10. Inactivation of tumor-Suppressor gene genes involved in lung cancer pathogenesis: p53, RB, RASSF1A, SEMA3B, SEMA3F, FUS1, p16, LKB1, RAR, and FHIT. tumor-acquired inactivating mutation of one allele tumor –acquired inactivation of expression by tumor-acquired promoter DNA methylation tumor cell with only the functionally inactive allele loss of function of the growth- regulatory tumor-suppressor gene

11. expresses nicotinic acetylcholine receptor  nicotine activates signaling pathway in tumor and normal cell that blocks apoptosis  involvement of nicotine directly in lung cancer pathogenesis both as a mutagen and tumor promoter Inherited Predisposition to Lung Cancer -People with inherited mutation on RB and p53 gene may develop lung cancer. -First degree relative of lung cancer probands have a two to threefold excess risk of lung cancer or other cancer, many of which are not smoking-related.