What is the recommended lab workup for a pulmonary mass suggestive of malignancy?

Lab Workup for Pulmonary Mass Suggestive of Malignancy

For a pulmonary mass suggestive of malignancy, obtain CT chest with contrast extending through the liver and adrenal glands, followed by tissue diagnosis via the least invasive method dictated by the clinical presentation, with sufficient tissue for both histologic typing and molecular analysis. 1, 2

Initial Laboratory and Imaging Studies

Essential Baseline Studies

• CT chest with contrast is the foundational imaging study for all patients with known or suspected lung cancer 2
• Extend CT imaging to include the liver and adrenal glands if PET scan is unavailable 2
• Obtain PET/CT for extrathoracic staging in patients with normal clinical evaluation and no suspicious findings on chest CT, except for brain 2
• Perform brain MRI or CT if metastatic workup is indicated or if prophylactic cranial irradiation is being considered 1

Routine Laboratory Tests

• Complete blood count (CBC) with platelets to assess for anemia, neutropenia, or thrombocytopenia 1
• Comprehensive metabolic panel including electrolytes, liver function tests (LFTs), calcium, BUN, and creatinine 1
• Lactate dehydrogenase (LDH) level, as elevated LDH is a prognostic factor in inoperable patients 1

Specialized Serum Markers (Context-Dependent)

• For suspected mesothelioma: serum mesothelin-related peptide levels may correlate with disease status 1
• For suspected small cell lung cancer: neuron-specific enolase and progastrin-releasing peptide may aid diagnosis when tissue is unavailable 3
• For adenocarcinoma: carcinoembryonic antigen (CEA) and CYFRA 21-1 may help with differential diagnosis and monitoring 3
• For squamous cell carcinoma: squamous cell carcinoma antigen may be useful 3

Important caveat: Serum biomarkers should not replace tissue diagnosis but may supplement when tissue cannot be obtained 3

Tissue Diagnosis Strategy

Algorithm Based on Clinical Presentation

For suspected small cell lung cancer (based on radiographic and clinical findings):

• Use the least invasive method available 1, 2:
  • Sputum cytology if productive cough present 1, 2
  • Thoracentesis if pleural effusion accessible 1, 2
  • Fine needle aspiration of supraclavicular node or accessible metastatic site 1, 2
  • Bronchoscopy with or without transbronchial needle aspiration (TBNA) 1, 2

For extensive mediastinal infiltration without distant metastases:

• Choose the least invasive safe method 1, 2:
  • EBUS-guided needle aspiration (preferred for mediastinal nodes) 1, 2
  • Bronchoscopy with TBNA 1, 2
  • EUS-guided needle aspiration 1, 2
  • CT-guided transthoracic needle aspiration (TTNA) 1, 2
  • Mediastinoscopy if endoscopic methods are negative or non-diagnostic 1

For solitary extrathoracic metastasis:

• Obtain tissue confirmation of the metastatic site if FNA or biopsy is feasible 1

For multiple distant metastases where biopsy would be technically difficult:

• Diagnose the primary lung lesion by the least invasive method 1

Pleural Effusion Protocol

• First step: Ultrasound-guided thoracentesis for cytologic assessment 1, 2
• If cytology negative: Proceed to pleural biopsy via 1, 2:
  • Image-guided pleural biopsy
  • Medical thoracoscopy
  • Surgical thoracoscopy (preferred for definitive diagnosis) 1
• Optional: Second thoracentesis may increase diagnostic yield before proceeding to biopsy 1

Critical point: If CT shows pleural thickening or pleural nodules/masses, consider image-guided needle biopsy as the first step 1

Central vs. Peripheral Lesions

For central lesions:

• Bronchoscopy is recommended to confirm diagnosis 1
• Perform further testing if bronchoscopy is non-diagnostic and suspicion remains 1
• Newer navigational techniques (radial EBUS, electromagnetic navigation) improve sensitivity for peripheral lesions 1

For peripheral lesions:

• Bronchoscopy has low sensitivity and high false-negative rate for peripheral lesions 1
• Consider transthoracic needle aspiration, though it has higher pneumothorax risk 1
• If nodule is peripheral and <2 cm, transparietal fine needle biopsy is preferred 1

Tissue Adequacy Requirements

• Obtain sufficient tissue for complete characterization, including histologic typing and molecular analysis 2
• If initial specimen is inadequate, a second biopsy is necessary 2
• For adenocarcinoma, tissue must be adequate for EGFR mutation testing, ALK and ROS1 rearrangement testing, and PD-L1 expression 3
• Aim for large (>0.7 mm²) and multiple (>2) biopsies to achieve >70% concordance with final tumor classification 1
• The rate of "not otherwise specified" (NOS) classification after complete diagnostic workup should be <10% 1

Staging Workup

For Potentially Resectable Disease

• Mediastinoscopy or endobronchial/esophageal ultrasound-guided biopsy is recommended if surgical resection is being considered 1
• Video-assisted thoracic surgery can be considered if contralateral disease is suspected 1
• Laparoscopy to rule out transdiaphragmatic extension if suggested by imaging 1
• Chest MRI for specific indications (e.g., evaluating chest wall or vascular invasion) 1

Timing Considerations

• Obtain PET/CT before pleurodesis if possible, as talc causes pleural inflammation leading to false-positive FDG avidity 1

Common Pitfalls to Avoid

• Do not accept cytology diagnosis of SCLC without clinical correlation; obtain histologic confirmation if presentation is atypical 2
• Do not stop after negative TBNA alone; negative predictive value is insufficient and requires mediastinoscopy confirmation 2
• Do not rely on sputum cytology alone; it is not specific for lung cancer and histological confirmation is required 1
• Do not perform routine hematological and biochemical tests in place of thorough history and clinical examination; reserve for high-risk patients 1
• Do not use chest radiography for follow-up of small nodules, as most <10 mm are not visible 4
• Do not perform PET/CT for nodules <8 mm, as sensitivity is inadequate 1, 4

Multidisciplinary Approach

• Evaluate patients requiring multimodality therapy with a multidisciplinary team including pulmonary medicine, thoracic surgery, medical oncology, radiation oncology, palliative care, radiology, and pathology 2
• For mesothelioma specifically, management by a multidisciplinary team with MPM experience is recommended 1