TUMORS OF LUNG AND PLEURA

1. TUMORS OF LUNG AND PLEURA

2. TUMORS OF THE LUNG TYPES : • Carcinomas – 90-95 % • Carcinoids – 5% • Mesenchymal tumour – 2-5 %

3. HISTOLOGIC CLASSIFICATION OF MALIGNANT EPITHELIAL LUNG TUMORS • Squamous Cell Carcinoma • Small Cell Carcinoma • Adenocarcinoma Acinar, papillary, bronchiolo-alveolar, solid, mixed • Large Cell Carcinoma • Large Cell Neuroendocrine Carcinoma

4. Adenosquamous Carcinoma • Carcinomas with pleomorphic, sarcomatoid, or sarcomatous elements • Carcinoid tumor • Typical • Atypical . Carcinoma of salivary gland type . Unclassified Carcinoma

6. Etiology and pathogenesis • Several environmental factors are known to cause genetic damage that transform benign bronchial epithelium to neoplastic tissue

7. 1 -Tobacco Smoking • Overwhelming evidence • 87% lung carcinoma occurs in smokers • 10 fold greater risk – Average smoker • 60 fold greater risk – Heavy smokers • Passive smoking – 3000 deaths per year

8. Histologic sequence of events: • Normal epithelium • Squamous Metaplasia • Squamous Dysplasia • Carcinoma in situ • Invasive Carcinoma

10. Cytogenetics : • Mutations in p53 gene ( G: C > T: A) Carcinogens in cigarette smoke: • Polycyclic aromatic hydrocarbons – Benzopyrine • Phenol derivatives • Radioactive elements • Polonium – 210 • Carbon – 14 • Potassium - 40

11. Other Contaminants : • Arsenic • Nickel • Molds • Additives

12. 2 -Industrial Hazards • High dose Ionizing Radiation; High incidence in Hiroshima / Nagasaki atomic bomb survivors • Uranium – 4 times increased risk in nonsmoker uranium miners • Asbestos – 5 times increased risk in nonsmokers, 50-90 times in smokers • Latent period – 10-30 years

13. 3 -Air Pollution • Indoor air pollution – Radon • Increased incidence in miners .

14. Molecular Genetics -For all practical purposes, lung cancer is divided into two clinical subgroups : • a - Small Cell Carcinoma • b - Nonsmall Cell Carcinoma -Supported by some specific molecular lesions in each subgroup .

15. Oncogenes : • C-Myc • Kras • EGFR • c-MET • c-KIT

16. Tumor Suppression Genes : • p53 • RB1 • p16 ( INK 4a) • Genes on chromosome 3p (FHIT, RASSF 1A )

17. Small Cell Carcinoma Genes : • C-KIT • MYC N • MYC L • p53 • 3p ( Early genetic change ) • RB • BCL 2

18. Non Small Cell Carcinoma Genes : • EGFR • KRAS ( Late genetic change) • p53 • p16 INK4a

19. MORPHOLOGY • Origin : • ¾ in the hilus – Bronchi • ¼ in the periphery – Alveolar septal cells, terminal bronchioles

20. PRECURSOR LESION PHASE • ( Squamous metaplasia ,Dysplasia, Carcinoma in situ ) • Preceed invasive carcinoma • May last for many years • Asymptomatic • No X-Ray changes; Small lesion • Positive diagnostic test ; Cytology ( Sputum, Bronchial lavage fluid/ brushings )

21. PRECURSOR LESION

22. POST INVASION PHASE • Larger tumour mass • Symptomatic, obstruct major bronchus • Infection ( Pneumonia ) • Atelectasis . Grow inside the bronchus; fungating mass . Penetrate the wall of the bronchus into the peribronchial tissue

23. POST INVASION PHASE INVASIVE LESION

24. Cauliflower like intraparenchymal mass • Grey white, firm to hard • Yellowish white mottling and softening • Extension to pleural surface and cavity • Involve pericardium • Regional lymph node involvement (Tracheal, Bronchial, Mediastinal )

25. Metastasis • Via both lymphatics and hematogenous spread • May be the first manifestation • Any organ; most commonly • Adrenals ( 60 %) • Liver ( 30-50%) • Brain ( 20% ) • Bone ( 20% )

27. ADENOCARCINOMA • Malignant epithelial tumour with glandular differentiation or mucin production • Patterns of growth : • Acinar • Papillary • Bronchioloalveolar • Solid with mucin formation

28. ADENOCARCINOMA; CHARACTERISTICS Most common type in : • Woman • Non-smokers ( 75% v/s > 98% ) • Lesion more peripherally located • Smaller size • Slow growth • Early and widespread mets • Cytogenetics ; - K RAS ( Specific for adenocarcinoma ) - p53 , RB1, p16 - EGFR ( mutation, amplification ) - C-MET

31. Bronchioloalveolar Carcinoma • Arises in terminal bronchioloalveolar region • 1-9 % • Gross : • Single / multiple nodules in lung periphery • Solid, grey white areas like pneumonia

33. Bronchioloalveolar Carcinoma Histology : • Growth along the preexisting structures • Preservation of alveolar architecture • No stromal, vascular or pleural invasion Sub types : - Mucinous: Tall columnar cells with cytoplasmic / intraalveolar mucin - Non-mucinous: Columnar or cuboidal cells

35. SEQUENCE OF EVENTS -Atypical adenomatous hyperplasia (Well demarcated focus of cuboidal to low columnar epithelium) | -Bronchioloalveolar Carcinoma | -Invasive Adenocarcinoma (Poorly demarcated invasive lesion/tumor)

36. SQUAMOUS CELL CARCINOMA • Most common lung cancer in Males • Strong correlation with smoking • Arise from segmental bronchi HISTOLOGY : • Sheets / clusters of atypical squamous cells • Keratinization / squamous pearls varies with grade of tumour • Intercellular bridges

43. Histologic Grades : • Well differentiated • Moderately differentiated • Poorly differentiated Cytogenetics : - p53 mutation; Most common - RB1, p16 ( INK4a), EGFR • Alleles at 3p, 9p, 17p • EGFR overexpression

44. SMALL CELL CARCINOMA • Highly malignant tumour • Strong correlation to cigarette smoking (Only 1% in non-smokers) • May arise centrally or peripherally • No percursor / preinvasive lesion • Widely metastatic • Surgically incurable • Ectopic hormone production

45. Small Cell Carcinoma • Cytogenetics : - p53 mutation - RB1 mutation

48. Small Cell Carcinoma Histology : • Clusters of relatively small round/oval/spindle shaped neoplastic epithelial cells with scant cytoplasm, illdefined cell borders • Salt and pepper chromatin • Absent /inconspicuous nucleoli • Prominent nuclear molding • High mitotic count • Azzopardi effect • Necrosis

50. Small Cell Carcinoma Immunohistochemistry : • Synaptophysin • Chromogranin • CD 57 • Parathyroid hormone- like product Electron Microscopy : Dense core neurosecretory granules