1. Neoplasms of Lung and Pleura William K. Funkhouser, M.D. Ph.D. –x 3-1069 –Bill_Funkhouser@med.unc.edu

2. Neoplasms of Lung and Pleura Primary Neoplasms of Lung Primary Neoplasms of Pleura Metastatic Neoplasms to Lung and/or Pleura

3. Neoplasms of Lung and Pleura: Classification by Lineage Epithelial – most common Melanocytic Stromal Mesothelial

4. Benign Lung Neoplasms Hamartoma Squamous papillomatosis Pleomorphic adenoma (ENT)

5. Hamartoma Clin: Adolescence  adulthood None in newborns - not congenital Rad: Solitary nodule +/- popcorn calcification Peripheral > central Path: Gross: solitary, lobulated, cartilagenous Micro: normal tissues in excess/disarray

6. Hamartoma Solitary Pulmonary Nodule

7. Bivalved Hamartoma

8. Cartilage in excess and disarray

9. Malignant epithelial neoplasms (Carcinomas) Squamous cell carcinoma Adenocarcinoma Large cell undifferentiated carcinoma Small cell undifferentiated carcinoma

12. Lung Carcinomas: Epidemiology Estimated Incidence (2003): 172,000 (US) Estimated Mortality (2003): 157,000 (US) >85% of lung carcinoma deaths (and 30% of all cancer deaths) occur in cigarette smokers Risk = f(# cigarettes smoked), 15-30X in heavy smokers, 50-60X in asbestos workers who smoke Risk decreases with cessation of cigarette smoking: baseline after 15 years

13. USA Tobacco Use 25% of US adults smoke cigarettes M=F US adults consume 2,400 cigs/person/year 36% of US high school students smoke est. 1.8 million new smokers/year (65% < 18 yo)

14. Tobacco: Morbidity and Mortality Premature ASVD: major risk factor Emphysema: Linear with exposure: 7%/10 years Chronic bronchitis Carcinomas of pharynx, larynx, lung, esophagus, bladder, kidney Fetal tobacco syndrome

15. Tobacco: Chemistry 80% air, 20% gases and particulates Gases: CO, CO 2, formaldehyde, acrolein, methanol, phenol, anthracenes, pyrenes Nicotine: 1% of smoke 85% absorbed in lung equivalent to 1 mg IV

16. Tobacco: Chemistry Particulates: –resin cores in 0.5  M diameter water droplets –est. 10 9 particles/ml –50% deposited in and cleared by cilia – remainder: phagocytosis, lymphatic transport Overall: 4,000 chemical compounds, of which 43 are considered carcinogenic

17. Squamous cell carcinoma Clin: Smokers (98%) 20-30% of common carcinomas May secrete PTH-like compound Rad: central > > peripheral Path: Bronchi > Larynx > Trachea +/- Desmosomes (intercellular bridges) +/- Keratin production, e.g. keratin pearls

18. Normal

20. Squamous cell carcinoma

21. Squamous cell carcinoma in situRespiratory mucosa

22. Invasive Squamous Carcinoma Keratin Desmosomes

23. Metastatic squamous cell carcinoma to lymph node Normal lymph node lymphocytes Mets in subcapsular sinuses

24. Adenocarcinoma Clin: 30-40% of common carcinomas Most common carcinoma in non-smokers, but 80% of adenoCAs occur in smokers Rad: peripheral > central Path: +/- glands +/- mucin Bronchiolo-alveolar carcinoma subset

25. Adenocarcinoma Primary Pleural effusion

26. Adenocarcinoma Gland formation

27. Adenocarcinoma Mucin production (red on PASd stain)

28. Bronchioloalveolar carcinoma (BAC) Clin: Rising incidence (presently 20-25%) Not associated with cigarette smoking Rad: Peripheral, can be multifocal and bilateral Path: Lepidic (butterfly-like) growth pattern Mucinous or non-mucinous Unifocal or multifocal Distinction of multifocal primary from mets

29. Bronchiolo-alveolar carcinoma

32. Large cell undifferentiated carcinoma Clin: 10% of common carcinomas Rad: non-specific Path: H&E: Undifferentiated EM: ? adenocarcinomas cDNA microarrays: distinct disease

33. Large cell undifferentiated carcinoma

35. Non-Small Cell Lung Carcinomas: Prognostic variables Definitely: Stage, performance status, weight loss Possibly gender, ploidy, k-ras mutation, p53 protein accumulation Not age, histology

36. Small cell carcinoma Clin: Smokers 20 % of common carcinomas Ectopic ACTH, ADH, Eaton-Lambert, carcinoid s. Commonly high stage at presentation Responsive to chemo/RT, but low 5 yr survival Rad: Central in >90% Frequent metastases to LNs and distant sites Path: Malignant cytology No nucleoli High mitotic activity and necrosis

37. Small cell undifferentiated carcinoma At diagnosis Response to therapy

38. Small cell undifferentiated carcinoma Viable carcinoma Necrotic carcinoma

39. Small cell undifferentiated carcinoma

41. Metastatic small cell carcinomaNormal lymphocytes

42. Small Cell Lung Carcinoma: Prognostic variables Definitely: Stage, performance status Probably: Gender, age, # of metastatic sites

43. Neoplasms of Lung & Pleura: Classification by Lineage Epithelial Melanocytic Stromal Mesothelial Metastases

44. Mesothelioma Clin: Associated with asbestos exposure Rad: Diffuse pleural involvement May have associated effusion Path: Malignant Deeply invasive growth pattern Epithelial, spindle cell, or biphasic Immuno: Keratin (+) EM: long microvilli

45. Mesothelioma: PA Chest Visible C-P Angle Loss of C-P Angle = Pleural effusion or mass

46. Mesothelioma: CT Thickened pleura Normal thickness pleura

47. Normal thin pleura

48. Deeply invasive mesothelioma (cytokeratin immunostain)

49. Epithelioid cytology of this mesothelioma mimics adenocarcinoma

50. Adenocarcinoma Mesothelioma N. Weidner

51. Asbestos body (Ferruginous body)

52. Neoplasms of Lung & Pleura: Metastases Most common malignant neoplasms involving the lung Multiple nodules favor metastases over primary neoplasms (except BAC) Carcinomas Sarcomas Melanoma

53. Metastatic carcinomas Breast adenoCA GI adenoCA Renal adenoCA Head/neck squamous cell CA

54. Metastatic Breast CA Pleural Thickening due to Metastases +/- Pleural Effusion

55. Metastatic breast carcinoma

56. Metastatic colon carcinoma

57. Metastatic renal cell carcinoma

58. Metastatic ENT carcinoma

59. Metastatic sarcomas Osteosarcomas Soft tissue sarcomas

60. Metastatic osteosarcoma

61. Metastatic melanoma Clin: Extrapulmonary 1  melanoma much more common than pulmonary 1  No known 1  in 5-10% of cases Path: Variable architecture & cytology May be pigmented Use immunohistochemistry to confirm

62. Metastatic melanoma

63. Neoplasms of Lung and Pleura 1  Lung Neoplasms - Most are carcinomas 1  Pleural Neoplasms - Mesotheliomas Mets to Lung and/or pleura – All lineages possible

64. Thanks for your time. Questions?