Purpose or Case Report: DICER1 is an RNA endoribonuclease that plays a role in the biogenesis of microRNAs (miRNAs). These miRNAs regulate gene expression by suppressing the translation of messenger RNA (mRNA) into proteins. Dysfunction of this mRNA suppression can result in oncogenic transformation. Patients with germ-line mutations of the DICER1 gene are predisposed to the development of certain organ-based childhood neoplasms such as pleuropulmonary blastoma (PPB), cystic nephroma (CN), nasal chondromesenchymal hamartoma (NCMH), and other rare tumors.

Our case report describes a patient who presented with multiple primary tumors consistent with DICER1 syndrome but tested negative for germ-line DICER1 mutation. Somatic DICER1 mutation with resultant mosaicism resulting in this phenotypic presentation has been recently described (de Kock et al. J Med Genet 2015); however, this DICER1 mosaicism is an extremely rare phenomenon with very few cases reported in literature. Here we describe the radiographic manifestations of a patient with such mosaicism of DICER1.

Our patient was initially diagnosed with pulmonary cystic lesions on prenatal ultrasound. Initial non-contrast CT of the thorax was performed on the first day of life and showed cystic lesions in both the right middle and lower lobes. A predominant lesion in the right middle lobe contained multiple cystic and possibly solid components (Figure 1). The patient subsequently underwent right middle lobe cyst resection with a final pathologic diagnosis of Type I PPB.

At nine months of age, the patient experienced repeated episodes of intussusception. Colonoscopy showed multiple polyps that were removed and returned benign pathology. At two years of age, the patient was diagnosed with Type II PPB. MRI of the brain was performed at that time, which showed large hemorrhagic metastases in the brain (Figure 2). He underwent multiple brain mass resections as well as chemotherapy, radiation therapy, and stem cell transplant. Additionally, he was diagnosed with NCMH at 8 years of age.

Although our patient presented with multiple primary tumors that are characteristic of DICER1 germ-line mutation, genetic testing for germ-line DICER1 mutation yielded negative results. As this case illustrates, for patients presenting with this constellation of radiographic findings and pathologic diagnoses of characteristic rare organ-based neoplasms, further genetic testing for somatic DICER1 mutation mosaicism is necessary.
Methods & Materials:
Results:
Conclusions: