Lung Cancer PDF

# Lung Cancer ## Basic Principles - Most common cause of cancer mortality in the US; average age at presentation is 60 years. - Key risk factors are: - Cigarette smoke - Radon - Asbestos ### Cigarette Smoke - Contains over 60 carcinogens; 85% of lung cancer occurs in smokers. - Polyc...

# Lung Cancer ## Basic Principles - Most common cause of cancer mortality in the US; average age at presentation is 60 years. - Key risk factors are: - Cigarette smoke - Radon - Asbestos ### Cigarette Smoke - Contains over 60 carcinogens; 85% of lung cancer occurs in smokers. - Polycyclic aromatic hydrocarbons and arsenic are particularly mutagenic. - Cancer risk is directly related to the duration and amount of smoking ("pack-years"). ### Radon - Is formed by radioactive decay of uranium, which is present in soil. - Accumulates in closed spaces such as basements. - Responsible for most of the public exposure to ionizing radiation; 2nd most frequent cause of lung carcinoma in US. - Increased risk of lung cancer is also seen in uranium miners. ### Environmental Toxins - Include asbestos, coal-fueled stoves, and metals (arsenic, chromium, and nickel). ## Presenting Symptoms - Nonspecific (e.g., cough, hemoptysis, dyspnea, weight loss, and post-obstructive pneumonia). ## Imaging - Usually reveals a large, spiculated mass; however, a solitary nodule ("coin-lesion") can be seen. - Biopsy is necessary for a diagnosis of cancer. - Benign lesions may also produce a "coin-lesion", especially in younger patients. Examples include: - Granuloma - often due to Tb or fungus (especially Histoplasma in the Midwest). - Bronchial hamartoma - benign tumor composed of lung tissue and cartilage; often calcified on imaging. ## Lung Carcinoma Classically divided into 2 categories: - **Small cell carcinoma (15%)** - usually not amenable to surgical resection (treated with chemotherapy and radiation). - **Non-small cell carcinoma (85%)** - Usually amenable to surgical resection. - Major subtypes include: - Adenocarcinoma (50%) - Squamous cell carcinoma (30%) - Large cell neuroendocrine carcinoma (5%) - Carcinoid tumor (5%) ## Table 9.5: Cancers of the Lung | Cancer | Characteristic | Association | Location | Comment | |------------------------------------|-----------------------------------------------------------------------------------------------------------------------|-------------------------------------|--------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Small cell carcinoma | Poorly differentiated small cells with neuroendocrine differentiation, chromogranin positive | Small cell, smoker, central, syndrome | Central | Rapid growth and early metastasis; may produce endocrine (e.g., ADH or ACTH) or nervous system (e.g., Lambert-Eaton myasthenic syndrome) paraneoplastic syndromes | | Adenocarcinoma | Glands, mucin, or TTF-1 expression by immunohistochemistry (IHC) | Male smokers | Peripheral (Fig. 9.20B) | Adenocarcinoma in-situ exhibits columnar cells that grow along preexisting bronchioles and alveoli (Fig. 9.21); may present as pneumonia-like consolidation on imaging | | Squamous cell carcinoma | Keratin pearls, intercellular bridges (Fig. 9.22A.B), or p40 expression by IHC | Most common tumor in nonsmokers and female smokers | Central (Fig. 9.22C) | | | Large cell neuroendocrine carcinoma | Poorly differentiated large cells (no glands, mucin, TTF-1, keratin pearls, intercellular bridges, or p40) | Most common tumor in male smokers | Central or peripheral | | | Carcinoid tumor | Well differentiated neuroendocrine cells (nests); chromogranin positive (Fig. 9.23A.B) | Not significantly related to smoking | Central or peripheral; when central, classically forms a polyp-like mass in the bronchus (Fig. 9.23C) | Low-grade malignancy; rarely, can cause carcinoid syndrome | | Metastasis to lung | Most common sources are breast and colon carcinoma | N/A | Multiple "cannon-ball" nodules on imaging | | ## TNM Staging - **T - Tumor size and local extension** - Obstruction of SVC leads to distended head and neck veins with edema and blue discoloration of arms and face (superior vena cava syndrome). - Involvement of recurrent laryngeal (hoarseness) or phrenic (diaphragmatic paralysis) nerve. - Involvement of the sympathetic chain (ptosis, miosis, and anhidrosis; Horner syndrome) and brachial plexus (shoulder pain and hand weakness) is seen with apical tumors involving the superior sulcus (Pancoast tumor). - **N - Spread to regional lymph nodes (hilar and mediastinal)** - **M - A unique site of distant metastasis is the adrenal gland.** ## Overall - 15% 5-year survival; lung carcinoma often presents late. - Screening by low-dose CT recommended for patients with long smoking history. ## Testing for "driver mutations" guides systemic therapy in advanced disease. - EGFR mutations (erlotinib) or ALK translocation (crizotinib) may be present in adenocarcinoma; EGFR is especially common in Asian females who are non-smokers. - Testing for PD-L1 expression (pembrolizumab) guides immunotherapy in advanced disease; PD-L1 may be present in any non-small cell carcinoma.