Kent J. Blanke D.O. FACOS

1. Kent J. Blanke D.O. FACOS Bronchogenic Carcinoma

2. My Rules For Lung Masses I am taught to think the worst. Any lung mass is cancer until proven otherwise!!

3. Epidemiology Etiology/risk factors Pathogenesis Pathology Diagnosis Staging Management Surgical Management Prevention Bronchogenic Carcinoma

4. Quick Pearls • Lung Cancer is the leading cause of cancer death in both men and women in the United States. • Bronchogenic Carcinoma is divided into two subgroups: Small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). • Non-small-cell includes adenocarcinoma, squamous cell, and large cell cancers.

5. Quick Pearls • The correct tissue diagnosis is critical to determine the appropriate therapy. • Small cell lung cancer has a high response rate to chemotherapy and radiation, and is rarely treated by surgery alone. It is highly aggressive, and tend to metastasize. • Non-small cell lung cancer can be cured by surgery alone in certain stages and is not curable by chemotherapy alone.

6. Epidemiology • Lung cancer is the second most common cancer in the U.S. • It accounts for 15% of all cancers. • Lung cancer accounts for approximately one-fourth of all cancer deaths. • In 2000 the deaths attributed to lung cancer were 160,000, exceeding the combined total deaths of breast, prostate, and colorectal cancer.

7. Epidemiology • Historically lung cancer predominated in men, however with the increase in smoking rates among women, the estimated male to female ratio is 1.2 : 1

8. Etiology/Risk Factors • Cigarette Smoking • Asbestos exposure • Radon exposure • COPD • Other carcinogens

9. Cigarette Smoking • Cigarette smoking is the most important risk factor in the development of lung cancer. • Smokers have a 10-25 fold increase in lung cancer incidence compared to nonsmokers. • Cigarette smoking accounts for > 85% of lung cancer seen in the USA.

10. Cigarette Smoking • More than 40 carcinogens have been identified in cigarette smoke, some include: polycyclic aromatic hydrocarbons, nickel, vinyl chloride, aldehydes, catechols, peroxides, and nitrosamines. • Smoking cessation causes a gradual drop in lung cancer risk, but not a complete normalization of risk

11. Cigarette Smoking • After 10-15 years of abstinence from smoking the life long risk of lung cancer approximates that of a nonsmoker. • Second hand smoke contains a significant amount of carcinogens. • Second hand smoke increases the chances of developing lung cancer with a relative risk of 1.3

12. Asbestos Exposure • Inhalation of asbestos fibers may cause both pulmonary and pleural malignancies, including bronchogenic carcinoma (all 4 types) and pleural mesothelioma. • The relative risk of lung cancer in an asbestos worker is approx. five fold. • The lag between time of first exposure to asbestos and the development of cancer ranges from 20-30 years.

13. Radon Exposure • In the US, as many as 30,000 lung cancer deaths may be attributable to radon exposure each year. • Mining of radioactive ores was the first occupation to be linked to the development of lung cancer. • The alpha particles of radon daughters are believed to deliver significant radiation to bronchial epithelium. • Significant radon exposure produces a 15 fold increase in the risk of developing lung cancer

14. COPD • The presence of COPD defined as either air flow obstruction on PFTs or symptoms of chronic bronchitis increases the risk of lung cancer several fold. • COPD is a risk factor by itself and is not just a reflection of the number of cigarettes smoked.

15. Pathogenesis • The development of bronchogenic carcinoma follows a multi-step carcinogenesis process with the successive accumulation of mutations in a number of genes involved in regulating growth. • DNA damage occurs after exposure to carcinogens.

16. Pathogenesis • A progression of histologic change occurs. • 1. proliferation of basal cells • 2. development of atypical nuclei with prominent nucleoli • 3. stratification • 4. development of squamous metaplasia • 5. carcinoma in situ • 6. invasive carcinoma

17. Pathogenesis • Oncogenes (c-myc, N-ras, c-erbB-2) • Tumor suppresor genes ( p53, retinoblastoma gene Rb) • Abnormalities of p53 expression occur in up to 100% of SCLC and 75% of NSCLC.

18. Pathology • There is a slight preponderance of lung cancer developing in the right lung because the right lung has approx. 55% of the lung parenchyma. • Lung cancer also tends to develop more commonly in the upper lobes than the lower lobes.

19. Pathology • Squamous cell accounts for one-third of all lung cancers. Until recently it was the most common cell type. It has been surpassed by adenocarcinoma which makes up approx. 45%. • Large cell accounts for 15-20% of tumors. • Small cell makes up 20-25% of primary lung malignancies.

20. Squamous Cell • Squamous cell carcinoma tends to originate in the central airways. It’s origin in the bronchial epithelium explains the occasional occurrence of positive sputum cytology in the absence of chest radiographic abnormalities

21. Adenocarcinoma • Most of these tumors are peripherally located (75%). Tends to metastasize earlier than squamous cell. Due to the peripheral location of these tumors sputum cytology is rarely positive. • A subcategory of adenocarcinoma called Bronchioalveolar carcinoma also arises in the periphery. However, this sub type tends to be more indolent and offer a better prognosis. These tumors appear as interstitial infiltrates on radiograph and can be confused with infectious pneumonitis.

22. Large Cell • The location and behavior of large cell carcinoma is very similar to that of squamous cell carcinoma. • Two rare subtypes of large cell are the giant cell carcinoma assoc with peripheral leukocytosis, and clear cell carcinoma which resembles renal cell carcinoma.

23. Small Cell • Approximately 80% originate centrally. • They tend to expand against the bronchus causing extrinsic compression. • These tumors spread rapidly to regional hilar nodes, mediastinal lymph nodes, and distant sites especially bone marrow and the brain.

24. Diagnosis • Management of Solitary Pulmonary nodule • Symptomatic Presentation of Cancer Patients • Laboratory Evaluation • Imaging Evaluation • Obtaining Tissue Diagnosis

25. Management of Solitary Pulmonary nodules • A significant number of lung cancers are initially detected as asymptomatic radiographic abnormalities. • A solitary pulmonary nodule is defined as an asymptomatic mass within the lung parenchyma that is less than 3cm and is well circumscribed. • Overall 33% of these masses are malignant, and 50% are malignant if the patient is older than 50.

26. Management of Solitary Pulmonary nodules • Discovery of a new nodule on chest film should begin with the review of previous chest radiographs. • Lesions that are new or increasing in size should be treated as pulmonary malignancies.

27. Management of Solitary Pulmonary nodules • Fine needle aspiration should be performed • If FNA is positive then resection is recommended. • If the FNA is nondiagnostic, definitive treatment or other diagnostic measures should be undertaken. • A wedge resection of the nodule is not always possible and lobectomy may need to be utilized for both diagnosis and treatment • Mediastinal lymph node dissection should be performed as part of the definitive treatment.

28. Conservative treatment in certain populations • Patients with a mass unchanged for more than 2 years. Needs to be documented by serial radiography. • Patients with benign patterns of calcification such as hamartomas. • Patient with masses clearly caused by inflammatory causes.

29. Symptomatic Presentation of patients • Patients are usually 50-70 years of age. • Lung cancer is clinically silent for most of it’s course. The presentation of symptoms is associated with later-stage disease and a worse prognosis. • Most patients have bronchopulmonary symptoms: cough(75%), dyspnea(60%), chest pain(50%), and hemoptysis(30%).

30. Cough 75% Weight loss 68% Dyspnea 60% Chest pain 50% Sputum production 45% Hemoptysis 30% Malaise 26% Bone pain 25% Lymphadenopathy 23% Fever 21% Hepatomegaly 21% Clubbing 20% Neuropathy 10% Superior Vena Cava 4% syndrome Dizziness 4% Hoarseness 3% Asymptomatic 12% Signs and Symptoms

31. Symptomatic Presentation of patients • Other symptoms may include hoarseness, superior vena cava syndrome, chest wall pain, Horner syndrome, dysphagia, pleural effusion, or phrenic nerve paralysis. • Nonspecific symptoms such as anorexia, malaise, fatigue, and weight loss may occur in 70% of patients.

32. The Silent Killer • Because the pulmonary parenchyma does not contain nerve endings, many lung cancer grow to a large size before they cause local symptoms (hemoptysis, change in sputum production, dyspnea, obstruction, or pain).

33. Cough • Either a new cough or a change in the nature of a chronic cough is the most common presenting symptom of bronchogenic carcinoma. • This symptom in a smoker should always cause concern.

34. Hemoptysis • Hemoptysis, either gross or minor, commonly occurs when mucosal lesions ulcerate. • Although the most common cause of hemoptysis is bronchitis, this sign should always lead to further investigation.

35. Obstruction • Tumors that obstruct major airways can produce wheezing, and unilateral wheezing suggests a localized obstruction

36. Lung Abscess • Lung cancer is often associated with cavitation and lung abscess formation, due either to airway obstruction with postobstructive pneumonia or to necrosis of a large tumor mass. • Clinical signs particularly indicative of malignancy associated lung abscess include chronicity of symptoms, lack of high fever, and lack of leukocytosis.

37. Pleural Effusions • Pleural effusions occur in approx 10-20% of patients at the time of diagnosis. • It is the most frequent sign that a tumor is non-operable. • Invasion of the pericardium can lead to cardiac tamponade as well as arrhythmia.

38. Superior Vena Cava Syndrome • Due to obstruction of the superior vena cava either by tumor or associated thrombosis. • Should be treated promptly following establishment of tissue diagnosis.

39. Horner Syndrome • Results from involvement of the superior cervical ganglion. • Characterized by unilateral facial anhidrosis, ptosis, and miosis. • Hoarseness can occur from invasion of the recurrent laryngeal nerve either from the mass directly or by regional lymph nodes. • Hoarseness is most commonly assoc with unresectability.

40. Pancoast Syndrome • Occurs in tumors involving the apex and superior sulcus of the lung. • Results from local invasion into the brachial plexus as well as the cervical sympathetic chain. • Clinical manifestations are dominated by shoulder and arm pain. • Can include Horner Syndrome and superior vena cava syndrome. • Delay in diagnosis is common due to the musculoskeletal component.

41. Digital Clubbing • Digital clubbing is seen in a variety of pulmonary conditions but occurs most commonly in association with bronchogenic carcinoma.

42. Other poor prognostic indicators • Esophageal obstruction • Vertebral body invasion • Distant extrathoracic tumor effects commonly involving lymph nodes, CNS, liver, bone and bone marrow, and the adrenal glands

43. Paraneoplastic Syndromes • Occur in 10% of patients with bronchogenic carcinoma. • Can be divided into systemic, endocrine, neurologic, cutaneous, hematologic, and renal categories.

44. Endocrine Abnormalities • Are relatively common in lung cancer. • Hypercalcemia is most commonly assoc with squamous cell and may occur directly due to bone invasion or indirectly due to Parathyroid Hormone. • SIADH and Cushing syndrome can be associated with small cell. • Elevations in ACTH may be found in 30-50% of small cell carcinomas. • Cushing syndrome is manifested by muscle weakness, hypokalemia, metabolic alkalosis, and diabetes.

45. Neurologic disorders • There is an association between small cell lung cancer and the Eaton-Lambert Myasthetic syndrome. • This syndrome is characterized by proximal muscle weakness, decreased or absent deep tendon reflexes, paresthesias, and autonomic dysfunction.

46. Laboratory Evaluation • CBC • Electrolyte panel • Liver function tests • Serum calcium assay • Tumor Markers

47. Tumor Markers • Carcinoembryonic antigen (CEA) • Creatine Kinase BB (CK-BB) • Neuron-specific enolase (NSE) • Bombesin/gastrin-releasing peptide (GRP) • Tissue Polypeptide antigen (TPA) • CA-125 • NSE and CEA are the markers used most frequently.

48. Imaging Evaluation • Chest X-ray • Computed Tomography • Magnetic Resonance Imaging • Positron Emission Tomography • Bone Scan

49. Imaging Evaluation • Radiologic evaluation is an integral part of the diagnosis and treatment of lung cancer. • Chest radiography and CT of the chest and upper abdomen to assess Liver and adrenals are the standard for initial imaging. • Bone scan and MRI of the brain are reserved for organ specific or nonspecific symptoms.

50. Imaging Evaluation • CT and MRI can identify the location of the primary tumor with respect to the other mediastinal structures. • However, it is difficult to determine if the mass merely abuts adjacent structures or if it invades them. • Often this distinction can only be made at the time of surgical exploration.