To investigate the clinicopathologic and radiologic features of pulmonary hamartomas (PHs) with uncommon clinical presentation.
A retrospective clinicopathologic and radiologic review was performed for patients diagnosed (1999-2019) with multiple hamartomas, lesions arising adjacent to a coexisting pulmonary malignancy, and tumors with predominantly extrapulmonary localization.
Of 979 patients diagnosed with PHs, 6 (0.6%) had multiple hamartomas, 4 (0.4%) had hamartomas adjacent to lung adenocarcinoma, and 2 (0.2%) had large mediastinal masses. Patients with multiple lesions had a median age of 65 years and mean tumor size of 0.9 cm; 1 patient had 3 hamartomas, and 5 patients had 2. Lesions next to adenocarcinomas had a mean size of 1.4 cm, and affected patients had a median age of 69 years. Predominantly mediastinal PHs, diagnosed in a 63-year-old woman and a 68-year-old man, measured 4.1 to 6 cm and were connected to the lung. All lesions were solid on imaging with absence of definitive fat or calcification, concerning for granuloma or malignancy. All cases had typical histology of PH, although one of the mediastinal tumors had an unusual amount of epithelial hyperplasia.
PHs can be clinically and radiologically challenging to diagnose. Histopathologic examination of biopsies and resection specimens is diagnostically crucial in this setting.

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