Lung Cancer Diagnostics

Laboratory Tests and Ancillaries

Laboratory tests to be requested should include electrolytes, liver function tests (LFTs), calcium, lactate dehydrogenase (LDH), blood urea nitrogen (BUN), and creatinine as these may be helpful for risk factor assessment.  

Pathologic Confirmation  

Rapid On-Site Evaluation (ROSE)  

The rapid on-site evaluation is used to accompany invasive procedures if possible.  

Sputum Cytology  

Due to poorly controlled sample collection, the diagnostic yield tends to be low for sputum cytology. It should be reserved for patients in whom bronchoscopy or fine needle aspiration biopsy (FNAB) is contraindicated.  

Histologic Diagnosis  

Please see Histologic Diagnosis under Classification for further information.  

Immunohistochemistry (IHC)  

Immunohistochemistry aids in distinguishing primary lung cancer from secondary metastases and in the determination of the specific subtype of NSCLC and SCLC. Immunohistochemistry stains used include thyroid transcription factor 1 (TTF1), napsin A, p40, and p63. For the specific types, TTF1 and napsin A are used for adenocarcinoma; p40 and p63 are used for squamous cell carcinoma; and if neither TTF1 nor p40 is positive, then it is considered as NSCLC-NOS.  For SCLC, Insulinoma-associated protein 1 (INSM1), CD56/NCAM, synaptophysin, and chromogranin A are used.    

Genotyping Analysis  

Molecular typing for the following mutations/alterations are also recommended: 

• Gene mutations: Epidermal Growth Factor Receptor (EGFR), Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2)/HER2
• Point mutations: B-Raf proto-oncogene (BRAF), KRAS proto-oncogene (KRAS)
• Gene rearrangements: Anaplastic lymphoma kinase (ALK), ROS proto-oncogene (ROS1), rearranged during transfection (RET)
• Mesenchymal-epithelial transition (MET) exon 14 (METex14) skipping variants
• NRTK1/2/3 (neurotrophic tyrosine receptor kinase) gene fusions

It must be noted that testing should be conducted as part of broad molecular profiling. 

Imaging

Non-invasive Imaging Procedures  

Chest X-ray  

A chest x-ray should be performed in all patients in whom lung cancer is suspected but should not be used alone as a screening tool. It does not have enough sensitivity to determine lymph node involvement. The usual findings in lung cancer include solitary pulmonary nodule, pulmonary or hilar mass, poorly resolving pneumonia, and pleural effusion.  

Chest Computed Tomography (CT) Scan  

Chest CT scan defines the size, location, and characteristics of a pulmonary mass (for staging purposes), determines the presence of lymphadenopathy, and allows the evaluation of surrounding structures. It may also be used to evaluate the presence of pleural effusion. It is the standard imaging procedure for determining metastasis.  

Low-dose CT (LDCT) is the recommended screening tool to detect lung cancer among defined high-risk populations. It may lower lung cancer-specific mortality by 20%. Multidetector CT may be considered for very small benign or malignant lung nodules.  

Positron Emission Tomography (PET) Scan  

PET scan determines normal from neoplastic tissues even as small as 1 cm. It may be performed in patients with solitary lung lesions, and it can increase the accuracy of staging patients.  

Positive results are due to infection or inflammation, absence of lung cancer with localized infection, presence of lung cancer with post-obstructive infection, or presence of lung cancer with inflammation in the node, parenchyma, and pleura. False-negative results may be due to a small nodule, nonsolid nodule or ground-glass opacity (GGO), adenocarcinoma in situ, or carcinoid tumor. It is better than a CT scan for mediastinal staging in non-small cell lung carcinoma (NSCLC); however, it is not reliable in identifying brain and urinary tract metastases.  

PET/CT Scan  

PET/CT scan may be done to assess distant metastases (eg bone metastasis) and guide mediastinal evaluation. It is superior to PET scan alone and to other standard imaging but inferior in detecting metastases to the brain. It improves the target accuracy of radiation therapy in patients with significant atelectasis and in patients with contraindications to intravenous CT contrast. If PET/CT scan is not available, then a bone scan may be used as an alternative to identifying bone metastasis. Fluorodeoxyglucose (FDG)-PET/CT scan is useful for the evaluation of solitary lung nodules, intrathoracic pathological lymph nodes, and distant metastases.  

Brain Magnetic Resonance Imaging (MRI) Scan     

Brain MRI is preferred over a CT scan in identifying brain metastasis.  

Bone Scan  

A bone scan is used to survey bone metastasis, although it may be less sensitive in cases of purely lytic bone metastases.  

Invasive Procedures  

The least invasive technique that renders the highest yield should be chosen.  

Bronchoscopy  

Bronchoscopy is used for diagnosing and staging central and peripheral lung lesions. It may be used as a confirmatory test for suspected central lesions. It is a required procedure prior to surgical resection. Sampling can be done through transbronchial needle aspiration, transbronchial lung biopsy, transbronchial cryobiopsy, bronchial brushing, or bronchial washing. Electromagnetic guidance for bronchoscopy increases bronchoscopy sensitivity (60%), specificity (91%), and accuracy (67%) for peripheral lesions.  

Lung Cancer_Diagnostics