INTRODUCTION
Central nervous system (CNS) germ cell tumors (GCTs) make up <4% of primary pediatric brain tumors, with incidence rates increasing among males, individuals <20 years old and Eastern Asian populations.1 Central nervous system GCTs can be broadly classified as germinomas, nongerminomatous GCTs (NGGCTs) or teratomas.1 Based on histological components, NGGCTs can be classified into embryonal carcinomas, yolk sac tumors (YSTs), choriocarcinomas, GCTs with mixed components (mixed GCTs) or germinomas with syncytiotrophoblastic giant cells (STGCs).1Teratomas may be divided into mature teratomas, immature teratomas or teratomas with malignant transformation.1
Down syndrome (DS) has classically been associated with higher rates of blood cancers such as acute myeloid leukemia (AML).2The incidence of solid tumors in patients with DS is rare, yet GCTs have been found to make up a disproportionate number of intracranial tumors as compared to the general population.3 Though associations between CNS GCTs and DS have been reported, the small number of cases is limiting; the most recent literature review reported just 21 patients with CNS GCTs and DS, with almost all studies arising from Japan or China.4 This paucity of cases, particularly of those from Northern America, has limited our understanding of this patient population.
The standard of care for CNS GCTs includes a combination of surgery, platinum-based chemotherapy and radiotherapy (RT), with specific treatments varying by tumor subtype and individual institution.1 In patients with DS, treatment is complicated by their increased risk of developing acute and long-term treatment-related adverse effects. Patients with DS are at an increased risk of RT-related cognitive impairments and cerebrovascular disease given their baseline cognitive impairments, decreased cerebral volume and predisposition to degenerative neurologic disease.5,6 Moreover, it is well-documented that patients with DS are highly susceptible to toxicities related to standard chemotherapy drugs used in AML; these include treatment-related infection, mucositis from methotrexate therapy, anthracycline-induced cardiomyopathy and even fatal neurotoxicity.5,7
Due to the complexity of care and rarity of cases, a standard treatment approach that promotes both optimal survival and minimization of treatment-related adverse effects in patients with CNS GCTs and DS has not been established. Here, we describe a multi-national and multi-institutional retrospective analysis of patients diagnosed with DS and CNS GCTs, in addition to a review of the literature.