Lung Tumors Overview

Lung Tumors

• Roughly 95% of primary lung tumors are carcinomas.
• The remaining 5% include carcinoid, mesenchymal malignancies, lymphomas, and a few benign lesions.
• "Hamatoma" is the most common benign tumor, appearing as a small (1-4 cm) discrete coin lesion on imaging. It's composed of mature cartilage, fat, fibrous tissue, and blood vessels.
• Carcinoma of the lung is strongly associated with tobacco smoking.
• It's the leading cause of cancer-related death in high-resource countries.
• In the US, it was the leading cause of cancer deaths in men since 1987 and women since 1987.
• The 2022 American Cancer Society estimates included 237,000 new cases and 130,000 deaths.
• Peak incidence is in the fifties and sixties.

Carcinoma Types

• Four major histologic types: adenocarcinoma, squamous cell carcinoma, small cell carcinoma (subtype of neuroendocrine), and large cell carcinoma.
• Combinations of histologic patterns can occur.
• Squamous cell and small cell carcinoma have the strongest association with smoking.
• Adenocarcinoma is the most common primary lung tumor in recent years, in women, never-smokers, and individuals under 45.
• Lung carcinoma was historically classified as small cell (SCLC) and non-small cell (NSCLC).
• NSCLCs are more resectable and less responsive to chemotherapy.

Lung Carcinoma Pathogenesis

• Similar to other cancers, smoking-related lung carcinomas develop through a stepwise accumulation of driver mutations producing neoplastic cells with cancer hallmarks.
• Inactivation of tumor suppressor genes on chromosome 3 (3p) is a common early event.
• Mutations in TP53 and KRAS genes occur later.
• Genetic changes like loss of 3p are found even in benign bronchial epithelium of smokers, suggesting a "field effect" (mutagenized respiratory mucosa).
• Subsets of adenocarcinomas in nonsmokers show activating mutations in the EGFR receptor tyrosine kinase.
• These mutations and others involve downstream signaling pathways involving RAS, PI3K, and other signaling molecules.

Lung Carcinoma Carcinogens

• Cigarette smoking and environmental carcinogens are primary culprits.
• Approximately 90% of lung cancer cases occur in current or recent smokers.
• Increased risk is directly related to the amount and duration of smoking.
• Women are more susceptible to carcinogens in tobacco smoke than men.
• Other occupational exposures (uranium mines, asbestos, arsenic, chromium, nickel, vinyl chloride) contribute, often synergistically, with smoking.
• Genetic factors modify the mutagenic effect of carcinogens.

Lung Carcinoma Diagnosis

• The four major histologic types show varied microscopic characteristics, including location within the lung, growth pattern, and degree of differentiation.
• Adenocarcinoma is typically peripheral, growing slowly and widely metastasizing early.
• Squamous cell carcinoma is more common in men, central in location, and spreads to hilar lymph nodes earlier than other types.
• Small cell carcinoma is usually central, spreads rapidly (often before diagnosis), and is highly sensitive to chemotherapy.
• Large cell carcinoma is a diagnosis of exclusion; undifferentiated with no specific features.

Lung Carcinoma Treatment

• Early detection and resection are often crucial.
• Combination treatments (surgery, radiation, chemotherapy) can be beneficial, especially for early-stage disease.
• Targeted therapies and immunotherapies are showing promise for various subtypes (adenocarcinomas), especially with genetic profiling of the tumors.
• Prognosis varies widely with cancer type and patient factors, as determined in part by the extent of spread when diagnosed.

Nasopharyngeal Carcinoma

• A rare neoplasm strongly linked to Epstein-Barr Virus (EBV).
• It's highly prevalent in certain populations (Southern China).
• Nasopharyngeal epithelium infection by EBV can lead to tumor transformation.
• Three histologic variants: keratinizing squamous cell carcinoma, nonkeratinizing squamous cell carcinoma, and undifferentiated carcinoma (strongly linked with EBV).

Laryngeal Tumors

• A variety of epithelial and mesenchymal neoplasms can occur in the larynx.
• Vocal cord nodules, papillomas, and squamous cell carcinoma are the most common, often identified by hoarseness.
• Vocal cord nodules are usually (but not always) benign.
• Laryngeal papillomas are benign and often caused by human papillomavirus (HPV) types 6 and 11.
• Laryngeal carcinoma is primarily squamous cell carcinoma in nearly all cases and is associated with smoking and alcohol use.
• Location within the larynx (glottic, supraglottic, subglottic) affects prognosis due to variations in lymphatic drainage patterns.