What types of lung cancers do not show on Positron Emission Tomography (PET) scans?

Lung Cancers That May Not Show on PET Scan

Bronchioloalveolar carcinoma (now classified as lepidic-predominant adenocarcinoma) and mucinous adenocarcinomas frequently fail to demonstrate hypermetabolism on PET scanning, with nearly two-thirds of these lesions producing false-negative results. 1, 2

Specific Tumor Types with Poor PET Sensitivity

Lepidic-Predominant Adenocarcinomas (formerly BAC)

• PET misses approximately 60-65% of bronchioloalveolar carcinoma lesions, despite the test's overall reported sensitivity exceeding 98% for other lung cancer types 2
• These tumors grow along alveolar walls without destroying lung architecture, resulting in minimal metabolic activity detectable by FDG-PET 2
• The usual risk factors for bronchogenic carcinoma are less reliable for these subtypes, requiring heightened clinical suspicion 2

Mucinous Adenocarcinomas

• Mucinous adenocarcinomas demonstrate low FDG uptake due to their cellular composition and growth pattern 1
• These lesions require tissue diagnosis rather than reliance on PET findings for management decisions 1

Ground Glass Opacities

• Lesions presenting as ground glass opacities on CT do not require PET scanning for staging, as these typically represent low-grade adenocarcinomas with minimal metabolic activity 3
• The American College of Chest Physicians explicitly states that ground glass opacities and an otherwise normal chest CT do not warrant PET evaluation 3

Size-Related Limitations

Small Lesions (<1 cm)

• PET scanning is not indicated for diagnosis of malignancy in pulmonary lesions less than 1 cm due to limited spatial resolution 3
• The American College of Chest Physicians recommends PET only for solitary pulmonary lesions larger than 1 cm that are suspicious on initial imaging 3
• For nodules measuring less than 1 cm, clinical and radiological surveillance at 3,6,12, and 24 months is the appropriate management strategy 3

Peripheral Stage IA Tumors

• In patients with peripheral stage cIA tumors, a PET scan is not required for staging 3
• These small peripheral lesions have low rates of mediastinal involvement and distant metastases, making PET less cost-effective 3

Critical Management Implications

When PET is Negative but Suspicion Remains High

• For nodules >8 mm with unclear hypermetabolic state on PET, proceed directly to tissue diagnosis rather than assuming benignity 1
• Non-hypermetabolic malignant tumors may have favorable prognosis but still require either 2-year surveillance or biopsy to confirm benignity 1
• The high reported sensitivity of PET can create false security with negative scans, particularly for lepidic-predominant and mucinous subtypes 2

Tissue Diagnosis Requirements

• All abnormal scans should be confirmed by tissue biopsy to ensure accurate staging, and conversely, negative PET scans in clinically suspicious cases warrant tissue diagnosis 3
• Nonsurgical biopsy is appropriate when clinical pretest probability and imaging findings are discordant, or when probability of malignancy is low to moderate (10-60%) 1
• Surgical resection without prior biopsy is reasonable when there is strong clinical suspicion of stage I or II lung cancer despite negative or equivocal PET 1

Risk Stratification Approach

Alternative to PET Reliance

• Calculate pretest probability using validated clinical models such as the Brock model, incorporating age, smoking history, nodule size, spiculation, and upper lobe location 1
• Clinical factors including increasing age, pack-years smoked, and previous malignancy should guide decision-making when PET is negative or equivocal 1
• Radiologic factors including nodule diameter, spiculation, and pleural indentation provide additional risk stratification independent of PET findings 1

Common Pitfalls to Avoid

• Do not defer invasive testing solely based on negative PET in patients with significant smoking history and suspicious nodule morphology, particularly if the lesion has ground glass or part-solid characteristics 1, 2
• Avoid observation alone for lesions with high clinical suspicion despite negative PET, as this can delay diagnosis of potentially lethal but PET-negative cancers 2
• Ensure sufficient FDG uptake in the primary tumor before relying on negative mediastinal PET findings to bypass invasive staging 3