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Abstract Title: Cracking the Code Early: Type I PPB as the First Sign of DICER1 Syndrome in Infancy
Background The DICER1 gene encodes an endoribonuclease essential for microRNA (miRNA) processing, a key element of post-transcriptional gene regulation. Germline mutations in DICER1 cause a rare autosomal dominant tumor predisposition syndrome, predisposing individuals—primarily children and young adults—to a spectrum of neoplasms. Tumorigenesis typically involves a germline loss-of-function mutation followed by a somatic “hotspot” mutation in the RNase IIIb domain, impairing miRNA maturation and dysregulating gene expression.
Pleuropulmonary blastoma (PPB) is a hallmark tumor of this syndrome and often represents the initial clinical manifestation. PPB progresses histologically from cystic (Type I) to solid (Type III) forms, with earlier stages associated with better outcomes. DICER1-associated tumors may show primitive mesenchymal features and various differentiations, including rhabdomyoblastic or cartilaginous elements. Due to the syndrome’s multi-organ involvement—including the lungs, kidneys, thyroid, ovaries, and brain—early detection and genetic testing are vital in initiating timely treatment and identifying at-risk family members, including asymptomatic carriers.
Case Presentation A 1-month-old male presented to his primary care physician with respiratory distress. Chest X-ray identified a left lower lung mass, prompting PICU admission and subsequent lobectomy. Postoperative recovery was smooth. Pathologic review raised suspicion for Type I PPB, with some inconclusive areas suggesting early Type II. Referral to the International PPB/DICER1 Registry confirmed Type I PPB. Genetic testing via next-generation sequencing revealed pathogenic DICER1 variants: c.3630del in exon 21 and c.5438A>G in exon 25, confirming a diagnosis of DICER1 tumor predisposition syndrome. The patient continues to be followed by pediatric oncology and genetics. Plans are underway for long-term surveillance and genetic counseling for first-degree relatives.
Discussion This case highlights the importance of recognizing hereditary cancer syndromes like DICER1. This patient was diagnosed unusually early at 1 month—well before the typical 2–3 years for Type I PPB—it underscores the need for timely imaging in infants with unexplained respiratory symptoms. Early detection is key, as lower-grade lesions may be cured with surgery before progressing to more aggressive types.
The discovery of pathogenic DICER1 mutations transformed the clinical focus to lifelong surveillance for associated tumors and risk assessment for relatives. Although targeted therapies are lacking, identifying DICER1 syndrome early allows for multidisciplinary care that can improve outcomes and reduce morbidity. For clinicians, maintaining a high index of suspicion for DICER1 syndrome in the presence of early-onset, cystic, or rare tumors is key to improving outcomes and reducing the burden of undiagnosed familial cancer syndromes.
