(113) Rare mutant-type DICER 1 embryonal rhabdomyosarcoma following precocious puberty and voice deepening: associations or red herrings?

Background: DICER 1 mutant-type embryonal rhabdomyosarcoma (ERMS) is rare. It has been recently proposed as a unique subset of DICER 1 rhabdomyosarcomas, which commonly present as soft tissue malignancies in children. These tumor mutations can be associated with germline DICER 1 syndrome. There is a known association with this syndrome and androgenizing ovarian tumors.

Case: We present the case of an 8 year old with a history of precocious puberty, who subsequently developed a vaginal mass. She had onset of vaginal bleeding at age 7. She underwent imaging with transabdominal pelvic ultrasound as part of her initial evaluation, which was unremarkable.

14 months later, she presented with ongoing spotting and tissue at the introitus. Ultrasound demonstrated a vascular 10 cm cystic mass in the vagina. She underwent resection, and pathology resulted as DICER 1-mutant sarcoma with features of ERMS, Botryoid type. Germline testing also eventually confirmed diagnosis of DICER 1 Syndrome.

Leading up to her presentation with a vaginal mass, she had significant voice deepening. She had no hirsutism or changes to her external genitalia. Androgens were normal on two rounds of testing.

She underwent chemotherapy with appropriate response. During the course of treatment she was found to have a heterogenous mass in the left ovary. Further evaluation with MRI was recommended, but parents wished to observe only. On subsequent surveillance ultrasound, this mass had involuted somewhat.

Comments: Mutant-type DICER 1 ERMS was only recently described as a distinct entity in 2021. It is thought to have favorable prognosis compared with wild-type DICER 1 ERMS. Both can be associated with germline DICER 1 mutations. This syndrome also has a known association with androgenizing Sertoli-Leydig ovarian tumors, among other rare tumors in children and adults.

Our patient had both precocious puberty predating her ERMS diagnosis, as well as voice deepening around the time of this diagnosis. She had no other signs of virilization, and androgens remained normal. She also had a somewhat atypical left ovarian mass, but this decreased in size on surveillance; we would not expect this to be an androgen producing sex cord stromal tumor, considering these factors. Further, there is no documented association between precocious puberty and DICER 1 Syndrome.

Based on current available data and studies from the patient, we suspect these were spontaneous and likely unrelated comorbidities. She remains at risk for adverse gynecologic outcomes, and will be monitored closely.