Neoplasms of Lung and Pleura

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. Solitary Pulmonary Nodule Hamartoma

7. Bivalved Hamartoma

8. Cartilage in excess and disarray Hamartoma

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, CO2, 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. 109 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 situ Respiratory mucosa

22. Desmosomes Keratin Invasive Squamous Carcinoma

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

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. Primary Pleural effusion Adenocarcinoma

26. Gland formation Adenocarcinoma

27. Mucin production (red on PASd stain) Adenocarcinoma

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

30. Bronchiolo-alveolar carcinoma

31. 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

34. 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. Response to therapy At diagnosis Small cell undifferentiated carcinoma

38. Necrotic carcinoma Viable carcinoma Small cell undifferentiated carcinoma

39. Small cell undifferentiated carcinoma

40. Small cell undifferentiated carcinoma

41. Normal lymphocytes Metastatic small cell carcinoma

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

46. Normal thickness pleura Thickened pleura Mesothelioma: CT

47. Normal thin pleura

48. Deeply invasive mesothelioma (cytokeratin immunostain)

49. Epithelioid cytology of this mesothelioma mimics adenocarcinoma

50. Adenocarcinoma Mesothelioma N. Weidner