Prevalence of lung cysts in adolescents and adults with a germlineDICER1pathogenic/likely pathogenic variant: a report from the National Institutes of Health and International Pleuropulmonary Blastoma/DICER1Registry

Abstract

BackgroundPleuropulmonary blastoma (PPB), the hallmark tumour associated withDICER1-related tumour predisposition, is characterised by an age-related progression from a cystic lesion (type I) to a high-grade sarcoma with mixed cystic and solid features (type II) or purely solid lesion (type III). Not all cystic PPBs progress; type Ir (regressed), hypothesised to represent regressed or non-progressed type I PPB, is an air-filled, cystic lesion lacking a primitive sarcomatous component. This study aims to evaluate the prevalence of non-progressed lung cysts detected by CT scan in adolescents and adults with germlineDICER1pathogenic/likely pathogenic (P/LP) variants.MethodsIndividuals were enrolled in the National Cancer Institute Natural History ofDICER1Syndrome study, the International PPB/DICER1Registry and/or the International Ovarian and Testicular Stromal Tumor Registry. Individuals with a germlineDICER1P/LP variant with first chest CT at 12 years of age or older were selected for this analysis.ResultsIn the combined databases, 110 individuals with a germlineDICER1P/LP variant who underwent first chest CT at or after the age of 12 were identified. Cystic lung lesions were identified in 38% (42/110) with a total of 72 cystic lesions detected. No demographic differences were noted between those with lung cysts and those without lung cysts. Five cysts were resected with four centrally reviewed as type Ir PPB.ConclusionLung cysts are common in adolescents and adults with germlineDICER1variation. Further study is needed to understand the mechanism of non-progression or regression of lung cysts in childhood to guide judicious intervention.