What low‑dose computed tomography (LDCT) findings indicate prior granulomatous infection in an older adult current or former smoker undergoing lung‑cancer screening?

LDCT Findings Indicating Prior Granulomatous Infection in Lung Cancer Screening

Calcified nodules with specific benign patterns—diffuse, central, laminated, or popcorn calcification—are the hallmark LDCT findings of prior granulomatous infection and require no further follow-up or investigation. 1, 2

Definitive Benign Calcification Patterns

The following calcification patterns on LDCT definitively indicate prior granulomatous infection (typically tuberculosis or histoplasmosis) and exclude malignancy:

• Diffuse calcification throughout the entire nodule indicates healed granulomatous disease and requires no surveillance 1, 2
• Central calcification (dense calcific focus in the nodule center) represents a healed granuloma and needs no follow-up 1, 2
• Laminated calcification (concentric rings of calcium) is pathognomonic for benign granulomatous disease 1, 2
• Popcorn calcification (irregular clumps resembling popcorn) typically indicates a hamartoma but can also represent old granulomatous infection 1, 2

Additional Benign Nodule Characteristics

Beyond calcification patterns, other LDCT features suggest prior granulomatous disease:

• Perifissural nodules (homogeneous, smooth, solid nodules with lentiform or triangular shape within 1 cm of a fissure, <10 mm) represent intrapulmonary lymph nodes from prior granulomatous exposure and require no follow-up 1, 2
• Subpleural nodules with the same morphology (smooth, triangular, <10 mm, within 1 cm of pleural surface) also represent benign lymph nodes and need no surveillance 1, 2

Critical Imaging Technical Requirements

To accurately identify these benign patterns, LDCT must be performed with specific technical parameters:

• Thin-section reconstruction of ≤1.5 mm (preferably 1.0 mm) is mandatory to characterize calcification patterns accurately 2
• Coronal and sagittal reconstructions should be routinely archived to facilitate nodule localization and characterization 2
• Thick slices (>3 mm) cause volume averaging that can obscure calcification patterns and lead to mischaracterization 2

Geographic Considerations and False-Positive Rates

In populations with high prevalence of granulomatous disease (endemic tuberculosis or histoplasmosis regions), LDCT screening produces significantly higher rates of positive scans without proportionally increasing cancer detection:

• The First Brazilian Lung Cancer Screening Trial demonstrated 39.4% positive LDCT scans (nodules >4 mm) compared to 26.9% in the National Lung Screening Trial, yet cancer prevalence was similar (1.3% vs. 1.0%) 3
• This 46% increase in positive findings was attributed to high prevalence of granulomatous disease from tuberculosis and fungal infections 3
• The positive predictive value was lower in the high-granulomatous-disease population (3.2% vs. 3.8%) 3

Pitfalls: When Granulomas Mimic Malignancy

Not all granulomatous nodules are calcified or obviously benign—active or recent granulomatous infections can produce nodules that are indistinguishable from lung cancer on LDCT:

• Non-calcified granulomas require the same risk stratification and follow-up as potentially malignant nodules 3
• PET-positive granulomas occur frequently because active granulomatous inflammation (tuberculosis, fungal infections, sarcoidosis) causes FDG uptake with SUVmax often ≥2.5, mimicking malignancy 1, 4
• Mycobacterial granulomas with SUVmax ≥2.5 were identified in multiple studies, demonstrating that PET cannot reliably distinguish active infection from cancer 4
• Size matters: Granulomas >30 mm are more likely to be culture-positive for mycobacteria and may require tissue diagnosis to exclude malignancy 4

Algorithmic Approach to Nodules in Screening Populations

When evaluating nodules on LDCT in older adult smokers:

1. First, assess for definitive benign calcification patterns (diffuse, central, laminated, popcorn) or typical perifissural/subpleural morphology—if present, no follow-up is needed 1, 2

2. For non-calcified nodules ≥8 mm, apply validated risk prediction models (Brock model preferred) that incorporate clinical factors (age, smoking history, prior cancer) and radiologic features (size, spiculation, upper lobe location) 1, 2

3. In endemic granulomatous disease regions, expect higher false-positive rates but maintain the same management algorithm—do not lower the threshold for biopsy simply because granulomatous disease is common 3

4. PET-CT cannot reliably distinguish active granulomatous infection from malignancy in nodules ≥1 cm, as both produce FDG uptake; tissue diagnosis may be required for PET-positive nodules without benign calcification 1, 4

5. For nodules requiring tissue diagnosis, be aware that granulomas can coexist with malignancy, and non-diagnostic biopsies (occurring in 6-20% of cases) do not exclude cancer 2, 5

Common Diagnostic Errors to Avoid

• Do not assume all calcified nodules are benign—eccentric, stippled, or amorphous calcification can occur in malignancy and requires further evaluation 1
• Do not rely on PET-CT alone to exclude malignancy in regions with high granulomatous disease prevalence, as false-positives are common 1, 3, 4
• Do not use chest radiography to characterize nodules or assess calcification patterns—CT with thin sections is required 2
• Do not extend surveillance intervals beyond guideline recommendations based on the assumption that a nodule "looks like" a granuloma without definitive benign calcification 2