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.