Childhood Rhabdomyosarcoma of the Female Genital Tract: Association with Pathogenic DICER1 Variation, Clinicopathological Features and Outcomes.

Abstract Objective : Rhabdomyosarcomas (RMS) of the female genital tract (FGT) have been recently found to be associated with germline pathogenic variation in DICER1, which can underlie a tumor-predisposition disorder. We sought to determine the incidence of pathogenic variation in DICER1 in a cohort of RMSs of FGT, as well as to evaluate the clinicopathological features and outcomes of the patients. Methods : We retrospectively reviewed medical records of the patients diagnosed with RMS of the FGT between 1990-2019. Molecular genetic sequencing of the tumor to detect an RNase IIIb domain hotspot mutation in DICER1 samples was performed in seven patients. Individuals with a missense mutation in the tumor were also screened for a loss of function germline mutation in DICER1. Results : Of 210 cases of pediatric RMS, 11 arose from the FGT. Molecular genetic sequencing of the tumor samples revealed a somatic missense mutation in the RNase IIIb domain of DICER1 in a total of three patients, two patients with embryonal RMS (ERMS) of cervix/uterus and one patient with ovarian ERMS. As a result of genetic testing for the loss of function germline mutation in DICER1, a heterozygous pathogenic variant was also found in two of these patients. Conclusions : Despite the limited number of patients, our findings suggest that it is important to be aware of the possible association between RMS of FGT and pathogenic germline DICER1 variants since the detection of this mutation in a patient or relatives can provide the opportunity for surveillance of related conditions that may improve long-term outcomes and survival.