Should a patient with bilateral 1–2 cm ground‑glass opacities, predominantly in the left lung base, undergo a biopsy?

Management of Bilateral 1–2 cm Ground-Glass Opacities at the Left Lung Base

For bilateral ground-glass opacities measuring 1–2 cm, biopsy is generally not recommended as the initial approach because diagnosis cannot be reliably confirmed by biopsy for pure ground-glass nodules, and the bilateral distribution with lower lobe predominance suggests a diffuse parenchymal process rather than focal malignancy. 1

Why Biopsy Is Not the First-Line Approach

Ground-Glass Nodules Have Poor Biopsy Yield

• For positive pure ground-glass nodules, diagnosis cannot be confirmed by biopsy, as stated in French expert consensus guidelines. 1
• CT-guided needle biopsy of ground-glass lesions has significantly reduced diagnostic yield compared to solid lesions, particularly for GGO-dominant lesions (51.2% vs 75.6% for solid-dominant lesions). 2
• Even when technically successful, the diagnostic accuracy of CT-guided core biopsy for GGO lesions is only 91%, with a false-negative rate of 8%. 3

Bilateral Distribution Changes the Differential Diagnosis

• Bilateral ground-glass opacities with lower lobe predominance are characteristic of diffuse parenchymal lung diseases (such as nonspecific interstitial pneumonia, organizing pneumonia, or hypersensitivity pneumonitis) rather than multifocal adenocarcinoma. 1
• The basal and bilateral distribution is consistent with usual interstitial pneumonia pattern or nonspecific interstitial pneumonia, which require different diagnostic approaches than focal nodules. 4, 5
• Upper lobe predominance would be atypical for common interstitial lung diseases and should raise suspicion for hypersensitivity pneumonitis or organizing pneumonia, but your patient has lower lobe involvement. 6

Recommended Diagnostic Algorithm

Step 1: Obtain Detailed Clinical Context

• Perform a comprehensive exposure history to identify potential causes: recent medications, organic antigen exposures (birds, mold, hot tubs), occupational exposures, and connective tissue disease symptoms. 6
• Assess for COVID-19 exposure or compatible symptoms, as COVID-19 can present with bilateral ground-glass opacities. 6
• Review smoking history and assess for symptoms of interstitial lung disease (progressive dyspnea, dry cough, bibasilar inspiratory crackles). 1, 5

Step 2: Short-Term Follow-Up CT

• Perform follow-up high-resolution CT in 3–6 months to assess for stability, progression, or resolution. 1
• Many ground-glass opacities are transient: 37.6% of pure GGO and 48.7% of mixed GGO lesions regress or disappear on follow-up, particularly when associated with infection or eosinophilic processes. 7
• If lesions resolve or significantly decrease, this suggests a benign inflammatory process (organizing pneumonia, eosinophilic pneumonia, or infection). 7, 8

Step 3: Consider Bronchoalveolar Lavage Before Biopsy

• Bronchoalveolar lavage (BAL) may be more informative than transthoracic biopsy for bilateral diffuse ground-glass opacities, as it can identify hypersensitivity pneumonitis (lymphocytosis), organizing pneumonia, or eosinophilic processes. 1, 6
• BAL is less invasive than surgical biopsy and can help narrow the differential diagnosis before proceeding to more invasive procedures. 1

Step 4: Surgical Lung Biopsy Only If Diagnosis Remains Uncertain

• If the HRCT pattern is indeterminate after follow-up and clinical correlation, surgical lung biopsy (preferably video-assisted thoracoscopic surgery) may be necessary to establish a definitive diagnosis. 1, 4
• Surgical biopsy is preferred over needle biopsy for diffuse parenchymal processes because it provides adequate tissue for histopathologic pattern recognition. 1
• The decision should be made at a multidisciplinary meeting involving pulmonologists, radiologists, and pathologists. 1, 4

When to Consider Malignancy (and Potentially Biopsy)

Features That Increase Suspicion for Multifocal Adenocarcinoma

• If one or more nodules are ≥1 cm with a solid component, the malignancy rate is significantly higher (93.3% for mixed GGO with solid component). 9, 7
• Spiculated margins, lobulated contours, or clear-cut margins are associated with malignancy. 1, 8
• Female sex and persistent nodules after 3–6 months of observation increase malignancy risk. 7, 8

Management of Suspicious Focal Nodules

• For focal ground-glass nodules ≥1 cm that persist after observation, surgical resection (sublobar resection or segmentectomy) is preferred over needle biopsy because biopsy cannot reliably confirm diagnosis and surgical excision is both diagnostic and therapeutic. 1, 9
• For nodules <2 cm with pure ground-glass opacity, atypical resection is initially recommended, with definitive management determined by final pathology. 1

Critical Pitfalls to Avoid

• Do not proceed directly to transthoracic needle biopsy for bilateral ground-glass opacities, as the yield is poor and the bilateral distribution suggests a diffuse process requiring different diagnostic approaches. 1, 2
• Do not dismiss the possibility of hypersensitivity pneumonitis or drug-induced pneumonitis, as these require immediate antigen/drug removal rather than biopsy. 6
• Do not assume all ground-glass opacities are malignant—nearly half of GGO lesions are transient and resolve with observation or antibiotics. 7, 8
• Do not delay follow-up imaging beyond 6 months for persistent nodules ≥1 cm, as this is the threshold where malignancy becomes highly probable. 9, 7