Brainstem Rhabdomyosarcoma Following Stereotactic Radiotherapy

Introduction: Neurofibromatosis type 2 (NF2) is a rare autosomal-dominant disorder characterized by the development of benign tumors of the peripheral and central nervous system (CNS), including schwannomas, meningiomas, and ependymomas. The gene responsible for the development of NF2 acts as a tumor suppressor gene. Stereotactic radiotherapy (SRT) and single fraction stereotactic radiosurgery (SRS) have been increasingly used over the past decades to treat benign tumors in patients with NF2. Proponents of SRT state that it is less invasive and can potentially be used to treat multiple tumors in a single session. The risk of inducing malignancy is unclear. Few reports exist of malignant peripheral nerve sheath tumors, meningiomas, or ependymomas occurring after SRT or SRS in NF2 patients. We present the first documented case of rhabdomyosarcoma (RMS) following SRT for multiple NF2-associated schwannomas.

Study Design: Case report.

Setting: Tertiary referral center.

Results: A 25-year-old woman with NF2 presented with symptoms of rapidly progressive brainstem compression 7 years after receiving SRT for the treatment of multiple posterior fossa schwannomas. A magnetic resonance imaging (MRI) study revealed a new large tumor involving the inferior right medulla. Surgery was undertaken to establish a diagnosis and to decompress the brainstem. Histology confirmed the diagnosis of embryonal RMS. Three months after the diagnosis, she succumbed to the disease. Genetic analysis of the RMS tumor demonstrated a normal karyotype. An NF2 mutation analysis on lymphocytes showed a constitutive germline deletion involving the NF2 promoter region and exon 1. A “second hit” NF2 mutation was not found by analysis of the DNA extracted from the RMS, which further suggests that the malignancy did not arise from a preexisting vestibular schwannoma (VS).

Conclusion: Both SRT and SRS remain attractive therapeutic options for patients with both sporadic and NF2-associated VSs. Over the last decade evidence has emerged indicating an increased risk of malignancy following radiotherapy, particularly in the NF2 patient population. During pretreatment consultation, patients should be counseled regarding the rare risk of developing a radiation-induced cancer. Although our findings do not argue against the use of SRT, they should heighten the awareness of postirradiation neoplasia and the need for individualized treatment.