Novel intronic DICER1 variation associated with pleuropulmonary blastoma in two siblings

Area of Science:

• Pediatric Oncology
• Genetics
• Thoracic Surgery

Background:

• Pleuropulmonary blastomas (PPB) are rare, aggressive pediatric lung cancers.
• PPB are frequently associated with germline DICER1 gene mutations.
• Early diagnosis and intervention are crucial for managing PPB.

Observation:

• Two pediatric cases of PPB are presented: a 2-year-old with a large right hemithorax mass (Type II PPB) and a 6-month-old sibling with a small cystic lesion (Type Ir PPB).
• The older sibling presented with upper respiratory symptoms, while the younger sibling underwent screening due to family history.
• Both patients were found to have the same novel, likely pathogenic DICER1 variant: c.2437-2A>G.

Findings:

• Pathological examination confirmed Type II and Type Ir PPB in the 2-year-old and 6-month-old, respectively.
• The 2-year-old received adjuvant chemotherapy, while the infant underwent surgical resection alone.
• Both patients are alive and well at 12 and 7 months post-treatment, respectively.

Implications:

• This study identifies a novel DICER1 variant associated with PPB, expanding the known spectrum of oncogenic mutations.
• The cases highlight the importance of genetic screening in families with a history of PPB.
• Successful outcomes in both cases underscore the effectiveness of tailored treatment strategies, including surgery and chemotherapy, for pediatric lung malignancies.