Non-metastatic causes of multiple pulmonary nodules

Various processes, including benign or malignant (mostly metastasis) processes, contribute to the occurrence of multiple pulmonary nodules. For differential diagnosis, metastasis must be excluded as an etiological factor in patients who have multiple pulmonary nodules with a known primary malignancy. However, differential diagnosis of multiple pulmonary nodules caused by benign diseases and malignant processes is challenging. Multiple pulmonary nodules resulting from metastasis may mimic those resulting from infections, inflammatory processes, and rare benign diseases. Some rare diseases, such as pulmonary sclerosing pneumocytoma and pulmonary epithelioid hemangioendothelioma, or common diseases with a rare presentation of multiple nodules must be considered in the differential diagnosis of metastasis. In addition to the clinical and laboratory findings, radiological features are crucial for differential diagnosis. The size, density, location, and border characteristics (well-defined or poorly defined) of pulmonary nodules, as well as their internal structure (solid, subsolid, or ground glass nodule), growth rate during follow-up, and associated pulmonary and extrapulmonary findings are important for differential diagnosis along with clinical and laboratory data. This article summarizes the general features and imaging findings of these diseases, which less frequently present with multiple pulmonary nodules, and the clues that can be used to distinguish these diseases from metastasis.