Case series reveals non-progressive cystic lung lesions harboring somatic RNase IIIb mutations in three siblings with germline DICER1 variants, indicating variable clinical behavior.
Key Points
Describe the clinical presentation, histopathological characteristics, and genetic profiles of non-progressive familial cystic lung lesions in siblings carrying DICER1 variants.
Clinical evaluation, radiological assessment with chest CT, and long-term surveillance of three male siblings from a single family.
Histopathologic analysis of surgically resected lung lesions alongside germline and somatic genetic sequencing targeting DICER1 alterations.
All three siblings shared an identical inherited paternal germline DICER1 frameshift variant, c.3630delC (p.Val1211Cysfs*28).
Somatic DICER1 RNase IIIb hotspot mutations (p.D1709G and p.D1810N) were identified in the resected CPAM type 4 lesions of the two surgically treated siblings without blastemal or malignant components.
The third sibling with bilateral small cystic lesions was managed conservatively and demonstrated stable disease without progression through 13 years of age.