What is the semiology of lung cancer?

Semiology of Lung Cancer

Lung cancer presents with a spectrum of clinical manifestations ranging from asymptomatic detection (25% of cases) to advanced symptomatic disease, with the majority presenting at stage IIIB or IV with symptoms from local tumor effects, intrathoracic spread, distant metastases, or paraneoplastic phenomena. 1

Primary Pulmonary Symptoms

The cardinal respiratory manifestations reflect direct tumor involvement of airways and lung parenchyma:

• Cough is the most common presenting symptom, occurring in 65% of patients at diagnosis, resulting from endobronchial irritation, parenchymal infiltration, or postobstructive pneumonia 1
• Hemoptysis occurs in 25-33% of patients and demands immediate evaluation for endobronchial tumor, particularly in smokers with COPD—even minimal blood-streaking warrants investigation as it may occur despite normal chest radiography 1
• Dyspnea affects approximately 17% at presentation, often accompanying postobstructive pneumonia or pleural involvement 1
• Chest pain occurs in 17.9% of patients; pleuritic pain specifically suggests pleural invasion 1
• Localized or unilateral wheezing indicates endobronchial obstruction and should prompt evaluation for neoplasm 1

Manifestations of Intrathoracic Spread

Local tumor extension produces characteristic syndromes based on anatomic involvement:

• Hoarseness from recurrent laryngeal nerve palsy (more common with left-sided tumors due to the nerve's circuitous route under the aortic arch), causing vocal cord paresis and predisposing to aspiration 1
• Pancoast syndrome from superior sulcus tumors includes shoulder/arm pain from brachial plexus invasion, Horner syndrome (ptosis, miosis, anhidrosis from sympathetic chain infiltration), and C8-T1-T2 distribution weakness and paresthesias 1
• Superior vena cava syndrome (lung cancer is the most common cause) presents with facial and neck swelling, dilated neck veins, prominent chest wall venous pattern, and occasionally dysphagia, cough, headache, or blurred vision 1
• Dysphagia from subcarinal adenopathy compressing the mid-esophagus 1
• Phrenic nerve dysfunction manifesting as elevated hemidiaphragm 1
• Pleural effusion causing dyspnea or chest pain, from direct tumor extension, metastatic implantation, or mediastinal lymphatic obstruction 1

Systemic and Metastatic Manifestations

Distant spread and systemic effects produce additional clinical features:

• Weight loss occurs in 8.3-33% of patients with OR 2.1 for lung cancer diagnosis within 6 months 1
• Fatigue affects 4.8% at presentation with OR 1.6 for diagnosis within 6 months 1
• Bone pain occurs in 5.9% initially (OR 2.7 at 6 months pre-diagnosis), suggesting skeletal metastases 1
• Headaches potentially indicate brain metastases 1
• Anemia from chronic disease or bone marrow involvement 1
• Paraneoplastic syndromes produce diverse manifestations 1

Histologic Classification and Clinical Correlation

The fundamental pathologic distinction between small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) remains critical, as it determines treatment approach and prognosis. 2

Small Cell Lung Cancer (SCLC)

• SCLC comprises 14% of all lung cancers (fewer than 20% per NCCN), with approximately 30,000 new cases annually in the United States 2, 3
• Almost all patients are heavy smokers, and the majority present with a perihilar mass causing peribronchial compression and obstruction 2
• Nearly all patients present in advanced stages with disseminated disease 2
• Morphologically, SCLC cells are small (two to three times the size of small lymphocytes) with scant cytoplasm, high nuclear-to-cytoplasmic ratio, nuclear molding, finely granular chromatin, and absent or inconspicuous nucleoli 2
• Interobserver agreement exceeds 95% when diagnostic criteria are satisfied 2

Non-Small Cell Lung Cancer (NSCLC)

NSCLC represents 85-90% of all lung cancers (more than 80-85% per NCCN guidelines) 3

Adenocarcinoma

• Adenocarcinoma is the single most common histologic subtype, accounting for approximately 40% of all lung cancers 3
• It is the most frequently occurring cell type in nonsmokers 3
• Adenocarcinomas tend to present in a peripheral location, show retraction or invasion of the visceral pleura, and are associated with tumor desmoplasia or scar 2
• Primary lung adenocarcinomas are typically TTF-1 positive, CK7 positive, and CK20 negative 2

Squamous Cell Carcinoma

• Squamous cell carcinoma represents approximately 30% of lung cancers and has the strongest association with tobacco smoking exposure 3
• Squamous cell carcinomas tend to present as near-hilar masses and are associated with bronchial metaplasia and squamous dysplasia 2
• They are found in cigarette smokers with radiologic imaging of COPD and histologic features of chronic bronchitis and emphysematous changes 2
• Squamous cell carcinoma is nonimmunoreactive for TTF-1 2

Large Cell Carcinoma

• Large cell carcinoma accounts for 5-10% of lung cancers 3

Clinical Presentation Patterns

Approximately 25% of patients are asymptomatic at diagnosis (typically with earlier-stage disease), while the majority present symptomatically with more advanced disease (stage IIIB or IV). 1

• Symptomatic patients are more likely to have concurrent COPD 1
• Lung cancer is usually suspected in individuals with abnormal chest radiograph findings or symptoms from local or systemic tumor effects 4

Molecular and Pathologic Considerations

The distinction between NSCLC subtypes, particularly adenocarcinoma versus squamous cell carcinoma, is now essential even on small biopsy samples or cytologic material (Grade 1B recommendation). 2

• Immunohistochemical panels using TTF-1 and/or napsin A support adenocarcinoma diagnosis, while p63 (or preferably p40) favors squamous cell carcinoma 2
• p40 (DNp63) is superior to p63 as a marker of squamous differentiation, with sensitivity and specificity reaching 100% 2
• Precise subclassification is achieved in most cases by conventional morphology, with immunohistochemistry recommended when routine histopathologic differentiation is difficult 2

Prognostic Context

Lung cancer remains the leading cause of cancer death worldwide, with 1,375,000 deaths annually and 157,000 deaths annually in the United States 2

• The overall 5-year survival for lung cancer remains at 16% (approximately 25.4% per recent data), significantly lower than other common cancers 2, 3
• Adenocarcinoma has a 32.2% 5-year survival rate 3
• Lung cancers are typically detected at an advanced stage, contributing to poor survival 2
• Smoking is responsible for approximately 80% of all lung cancer cases 3