Orbital tumor in DICER1 syndrome (embryonal tumor with multilayered rosettes) successfully treated with intraarterial chemotherapy

Purpose Ophthalmic malignancies are well described in DICER1 syndrome and include intraocular malignancies and, rarely, primary orbital tumors (or medulloepitheliomas). Here, we present the case of an aggressive primary orbital malignancy (embryonal tumor with multilayered rosettes [ETMR]) in a child with germline and somatic DICER1 abnormalities. Observations In a 1-month-old boy born at term, a computed tomography scan revealed an orbital mass initially thought to be consistent with a capillary hemangioma. After initial treatment with a 4-week course of oral propranolol (3 mg/kg/day) without response, a magnetic resonance imaging scan revealed an enlarging lobulated large enhancing left intraconal mass. A series of biopsies and DNA methylation array analyses showed the lesion to be an ETMR, atypical subclass. Germline analysis revealed a mutation in the DICER1 gene. The tumor itself had a second, different mutation in the DICER1 gene. ETMR has been rarely identified in the orbit and there are no accepted treatments, but overall survival of ETMR lesions is poor (<20%) with combinations of surgery, radiation, or brachytherapy. The family was offered exenteration but refused, so intraarterial chemotherapy was offered with the understanding that it had never been tried in DICER1 -mutated orbital ETMR. After treatment in 4 monthly 2-hour outpatient sessions with intraarterial chemotherapy, we observed prompt regression of clinical findings. Serial imaging following the final cycle of treatment demonstrated no evidence of recurrent or progressive disease. Twenty-three months later, there has been no regrowth. Conclusion and importance A somatic and germline (“two hit”) DICER1 -mutated orbital tumor was successfully managed without surgery, radiation, or systemic chemotherapy using the well-established intraarterial approach presently used for retinoblastoma. In the case of our patient, intraarterial chemotherapy proved to be an effective treatment for this tumor.