What is the differential diagnosis and management approach for a lung mass?

Differential Diagnosis for Lung Mass

A lung mass requires systematic evaluation to distinguish between malignant and benign etiologies, with the primary differential including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), metastatic disease, infectious granulomas, hamartomas, lung abscesses, and inflammatory conditions such as chronic eosinophilic pneumonia. 1, 2, 3

Primary Malignant Etiologies

Lung Cancer Categories

• Non-small cell lung cancer (NSCLC) accounts for the majority of lung malignancies and includes adenocarcinoma, squamous cell carcinoma, and large cell carcinoma 2
• Small cell lung cancer (SCLC) represents a distinct category with different treatment implications and typically presents with extensive mediastinal involvement 4
• Metastatic disease from extrathoracic primary tumors can present as solitary or multiple lung masses 4

Clinical Presentation Patterns

• Constitutional symptoms (fatigue, weight loss) or organ-specific symptoms (bone pain, neurologic symptoms) suggest metastatic disease 4
• Local invasion patterns include Pancoast syndrome or superior vena cava syndrome 5
• Paraneoplastic syndromes may be the initial manifestation 5

Benign Etiologies

Common Benign Masses

• Hamartomas are the most common benign lung neoplasms, characterized by fat density and "popcorn" calcification patterns on CT 4, 3
• Granulomas from infectious or inflammatory processes (tuberculosis, histoplasmosis, sarcoidosis) are among the most frequently encountered nonneoplastic masses 3, 6
• Lung abscesses present as cavitary lesions with air-fluid levels 7

Inflammatory Mimics

• Chronic eosinophilic pneumonia can masquerade as a lung mass and requires biopsy for definitive diagnosis 7
• Inflammatory pseudotumors and fibrous tumor-like lesions represent rare benign entities 3

Initial Diagnostic Approach

Imaging Strategy

• Obtain CT chest with contrast as the foundational imaging study, extending to include liver and adrenal glands if PET unavailable 1
• Perform thin-section CT through the nodule to characterize calcification patterns and fat content 4, 1
• Diffuse, central, laminated, or "popcorn" calcification patterns indicate benign disease requiring no further follow-up 4

Risk Stratification for Solid Nodules

• For nodules <6 mm: malignancy probability <1%; follow-up CT in 6-12 months based on risk factors 6
• For nodules 6-8 mm: malignancy probability 1-2%; repeat CT in 6-12 months 4, 6
• For solid nodules >8 mm: estimate pretest probability using clinical judgment or validated models 4, 1

Functional Imaging

• PET imaging is recommended for solid nodules ≥8 mm with low-to-moderate pretest probability (5%-65%) of malignancy 4, 1
• PET has approximately 97% sensitivity and 78% specificity for nodules ≥1 cm 6
• Do not perform PET for nodules with high pretest probability (>65%); proceed directly to tissue diagnosis or staging 4

Tissue Acquisition Strategy

Scenario-Based Diagnostic Algorithm

For suspected SCLC based on radiographic appearance:

• Use the least invasive accessible method: sputum cytology if productive cough present, thoracentesis if pleural effusion accessible, FNA of supraclavicular nodes, or bronchoscopy with TBNA 4, 1

For extensive mediastinal infiltration without distant metastases:

• Choose among EBUS-guided needle aspiration (93% diagnostic yield, 100% specificity), bronchoscopy with TBNA, EUS-guided needle aspiration, or CT-guided transthoracic needle aspiration 4, 1
• Critical pitfall: TBNA has only 71% negative predictive value; mediastinoscopy is mandatory for nondiagnostic results 4

For accessible pleural effusion:

• Begin with ultrasound-guided thoracentesis 4, 1
• If cytology negative, proceed to pleural biopsy via image-guided biopsy, medical thoracoscopy, or surgical thoracoscopy 4, 1
• Consider second thoracentesis before invasive pleural biopsy if first cytology is negative 4

For small (<3 cm) peripheral lesions in surgical candidates:

• When moderately to highly suspicious for malignancy, surgical excision via thoracoscopy provides both diagnosis and treatment 4
• For indeterminate probability, consider TTNA or bronchoscopy with radial EBUS or electromagnetic navigation (sensitivity 70-90%) 4, 6

For suspected metastatic disease:

• Biopsy the most accessible metastatic site when feasible to simultaneously establish diagnosis and stage 4, 1
• If metastatic sites are difficult to access but radiographically obvious (multiple brain, liver, or bone lesions), diagnose the primary lung lesion by the easiest method 4

Tissue Adequacy Requirements

• Obtain sufficient tissue for complete histologic typing and molecular analysis (EGFR, ALK, PD-L1 testing) 1
• Use 19-gauge needles for TBNA to provide better tissue samples for histologic evaluation 4
• If initial specimen inadequate, second biopsy is necessary and acceptable 1
• Avoid accepting cytology diagnosis of SCLC without clinical correlation; obtain histologic confirmation if presentation is atypical 1

Stability and Follow-Up Criteria

• Solid nodules stable for ≥2 years require no additional diagnostic evaluation 4
• This recommendation applies only to solid nodules; subsolid nodules require different follow-up protocols 4
• Ground-glass nodules persisting beyond 3 months and >10 mm have 10-50% malignancy probability 6

Multidisciplinary Coordination

• Assemble a multidisciplinary team including pulmonary medicine, thoracic surgery, medical oncology, radiation oncology, palliative care, radiology, and pathology for patients requiring multimodality therapy 4, 1
• Joint decision-making among radiologist, pulmonologist, and oncologist optimizes diagnostic approach selection 4