Interstitial lung disease (ILD) encompasses a diverse range of conditions that lead to inflammation and/or scarring of the lung interstitium, often affecting airspaces and resulting in a progressive decline in lung function. High-Resolution Computed Tomography (HRCT) is a crucial diagnostic tool for ILDs, and their characterization based on imaging. This article specifically focuses on ILD presentations characterized by small lung nodules on HRCT, defined as those measuring less than 10 mm. Small nodules on HRCT are analyzed based on size, distribution, borders, attenuation, associated findings, and temporal evolution to narrow diagnostic considerations. A key factor is the distribution pattern, which is placement within the secondary pulmonary lobule and axial interstitium. Based on their distribution pattern relative to the anatomical core of the lobule, small nodules are classified into 3 specific imaging phenotypes: perilymphatic, centrilobular, and random. Perilymphatic nodular phenotypes typically involve disease processes affecting the pulmonary lymphatics along the interlobular septa, pleura, fissures, and/or bronchovascular bundles. Common conditions include Sarcoidosis, Occupational lung diseases such as coal worker pneumoconiosis (CWP) and silicosis, Chronic beryllium disease, Granulomatous and Lymphocytic interstitial lung disease (GL-ILD), Pulmonary septal amyloidosis, Pulmonary alveolar microlithiasis, Diffuse Pulmonary Ossification. Centrilobular nodular phenotypes are centered on the core structures of the secondary pulmonary lobule, including bronchioles, pulmonary arterioles, and central lymphatic vessels. They can be nonbranching (solid or ground-glass attenuation) or branching, often appearing as a "tree-in-bud" morphology. Nonbranching centrilobular nodules are seen in conditions such as Nonfibrotic hypersensitivity pneumonitis (HP), Respiratory bronchiolitis (RB), Follicular bronchiolitis (FB), Lymphocytic interstitial pneumonitis (LIP), Metastatic pulmonary calcification (MPC), Pulmonary hemosiderosis, and Pulmonary Langerhans cell histiocytosis (LCH). Branching centrilobular nodules ("tree-in-bud") are typically not associated with ILDs and often indicate Infectious bronchiolitis, Aspiration and other disorders. Random pulmonary nodular phenotypes refer to nodules without a consistent relationship to the secondary lobule or other lung structures. While profuse perilymphatic nodules (e.g., in sarcoidosis and occupational lung diseases) can appear randomly distributed, true random patterns are characteristic of hematogenous infections or miliary metastases.
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