Pleuropulmonary blastoma and the challenge of distinguishing the cystic form (type I) from other congenital lung malformations

Abstract Pleuropulmonary blastoma is a rare pediatric lung tumor of mesenchymal origin, with prognosis varying by subtype. While types II and III are usually identifiable on imaging due to their solid tumor components, the purely cystic type I represents a particular diagnostic challenge. In imaging, it is often difficult to distinguish from benign congenital lung malformations such as congenital pulmonary airway malformation (CPAM, formerly congenital cystic adenomatoid malformation or CCAM), sequestration, or bronchogenic cyst. Accurate differentiation, however, is clinically relevant, as misclassification may lead to inadequate treatment or an increased risk of disease progression. This article highlights the role of imaging modalities (computed tomography, magnetic resonance imaging, including ultrashort echo time sequences), as well as histopathology and genetics—especially DICER1 mutation—in the diagnosis and therapeutic decision-making of pleuropulmonary blastoma. A modified flowchart based on Feinberg et al. provides practical guidance. For patients with pleuropulmonary blastoma carrying a DICER1 mutation, specific organ-targeted follow-up recommendations are provided to enable early detection of associated tumors. Graphical Abstract