Are pulmonary non-calcified granulomas benign?

From the Guidelines

Pulmonary non-calcified granulomas are generally considered benign lesions, but they require evaluation to rule out active infection or malignancy, and most patients with stable, incidentally discovered non-calcified granulomas do not require specific treatment, but addressing any underlying cause may be appropriate. These small nodules represent areas of inflammation where the body has walled off foreign material or infection. The lack of calcification typically indicates they are more recent formations compared to calcified granulomas, which represent older, healed lesions. Common causes include previous infections (particularly fungal infections like histoplasmosis or tuberculosis), sarcoidosis, or exposure to certain environmental substances.

Key Considerations

• When discovered incidentally on imaging, these nodules usually warrant follow-up imaging to ensure stability over time, as recommended by the Fleischner Society guidelines 1.
• If the granulomas show growth or concerning features, further investigation with additional imaging or biopsy may be necessary, and patients with known risk factors for lung cancer or those with symptoms should receive more thorough evaluation.
• The differential diagnosis of granulomatous diseases is broad, and histological features alone cannot distinguish sarcoidosis from other granulomatous diseases, as noted in the American Thoracic Society clinical practice guideline 1.
• A noncalcified solitary pulmonary nodule that cannot be proven to be stable for at least 2 years, or diminishing in size, should be considered to be a potential malignant lesion, and a full medical history and further evaluation with CT scan and/or PET scan may be necessary, as recommended in the IDSA clinical practice guideline 1.

Management Approach

• Follow-up imaging is recommended at approximately 3–6 months, followed by an optional second scan at 18–24 months, depending on estimated risk, as recommended by the Fleischner Society guidelines 1.
• Patients with clinical evidence of infection and those who are immunocompromised should be considered for active infection, and short-term follow-up may be appropriate.
• Addressing any underlying cause of the granuloma may be necessary, and patients should be educated about the nature of the illness, the need or lack of need for antifungal treatment, and the overall prognosis, as recommended in the IDSA clinical practice guideline 1.

From the Research

Pulmonary Non-Calcified Granulomas

• Pulmonary non-calcified granulomas can be caused by various factors, including infections, immunological conditions, and idiopathic conditions such as sarcoidosis 2, 3.
• The diagnosis of granulomatous lung disease requires familiarity with the tissue reaction as well as with the morphologic features of the organisms, including appropriate interpretation of special stains 2.
• Granulomas can be distributed along lymphatic routes, randomly, or along the airways, and their pattern of distribution within the secondary lobule can aid in diagnosis 3.

Benignity of Pulmonary Non-Calcified Granulomas

• There is no direct evidence to suggest that all pulmonary non-calcified granulomas are benign 2, 3, 4, 5, 6.
• However, some granulomatous diseases, such as sarcoidosis, can be benign and self-limiting, while others, such as infectious diseases, can be serious and require specific treatment 4, 5.
• The diagnosis and treatment of granulomatous lung disease require a multidisciplinary approach, including radiological, histopathological, and clinical evaluation 3, 4, 6.

Diagnostic Approach

• A combined radiological-histopathological approach is proposed for defining the morphological features and anatomic localization of granulomatous interstitial lung diseases 3.
• Thin-slice computed tomography (CT) is the standard imaging modality for the work-up of granulomatous diseases of the lungs, and can aid in diagnosis and detection of disease complications and comorbidities 6.
• Special stains and culture techniques for microorganisms or fungi are crucial to establish the specific etiologies of granulomatous inflammation of the lungs 2, 5.