Non-progressive DICER1-associated cystic lung lesions in three siblings with somatic RNase IIIb hotspot mutations: a case series

Introduction Familial occurrence of non-progressive cystic lung lesions in siblings carrying the same germline DICER1 pathogenic variant is extremely rare, particularly when somatic RNase IIIb hotspot mutations are identified in resected lesions. Case presentation Three male siblings from one family were evaluated. Case 1, the youngest, developed acute respiratory distress after umbilicoplasty at 13 months of age. Chest CT showed a large multilocular cystic lesion occupying the left hemithorax with mediastinal shift. Left upper lobectomy was performed, and histopathology demonstrated CPAM type 4 without blastemal or rhabdomyoblastic components. Case 2, the eldest, had an asymptomatic left upper lobe cystic lesion detected on chest radiography at 4 months of age. At 12 years, CT showed a 6.5 × 4.5 cm septated cystic lesion in the lingular segment. Segmentectomy was performed, and histopathology also demonstrated CPAM type 4 without malignant features. Case 3, the middle sibling, was asymptomatic. Surveillance CT at 7 years, after identification of the familial DICER1 pathogenic variant, revealed small bilateral cystic lung lesions. He was managed conservatively, and the lesions remained stable without progression at 13 years. All three carried the same germline DICER1 frameshift variant, c.3630delC (p.Val1211Cysfs*28), inherited from their father. Somatic DICER1 RNase IIIb hotspot mutations, p.D1709G and p.D1810N, were identified in the resected lesions of Cases 1 and 2, respectively. Conclusion Pulmonary cystic lesions associated with DICER1 alterations may show variable clinical behavior. Molecular testing may help characterize such lesions and inform surveillance and familial risk assessment.