Introduction
DICER1 syndrome is a cancer predisposition disorder characterized by a germline loss-of-function variant in DICER1 and an increased risk of developing multiple tumors, including pleuropulmonary blastoma (PPB), cystic nephroma, multiple thyroid nodules, and Sertoli–Leydig cell tumors1,2. Additionally, extremely rare tumors, including ciliary body medulloepithelioma, nasal chondromesenchymal hamartomas, and cervical embryonal rhabdomyosarcoma (ERMS), are also associated with DICER1 . Since DICER1 was revealed as a causative gene of familial PPB in 2009, the number of tumors recognized as DICER1 -associated has been increasing3. In most cases, somatic hotspot mutations in the DICER1 RNaseIIIb domain (p.E1705, p.D1709, p.D1809, p.D1810, and p.E1813) are detected in tumor tissue as a second hit1. Patients withDICER1 syndrome typically have truncated variants in the exonic regions of DICER1 1,4. DICER1 germline pathogenic variants are detected in approximately 80% of PPB patients, with the remaining cases considered sporadic4. However, DICER1 syndrome may be underdiagnosed because some cases of genomic alterations are missed by conventional genomic analysis techniques.
Here, we present a case of DICER1- related urogenital ERMS that developed in a male 13 years after the PPB diagnosis. The patient was initially diagnosed with sporadic PPB by whole-exome sequencing (WES); however, DICER1 complementary DNA (cDNA) analysis conducted at 16 years of age revealed a germline intronic variant, which led to theDICER1 syndrome diagnosis.