124  Other Embryonal and Pineal Malignancies of the Central

Nervous System
Emily Gertsch, Yoon-Jae Cho, and Scott L. Pomeroy

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INTRODUCTION TYPES OF CNS EMBRYONAL TUMORS

Embryonal tumors of the central nervous system (CNS) Embryonal Tumors with Multilayered Rosettes
are recognized as the most common types of malignant pedi-
Embryonal tumors with multilayered rosettes (ETMRs) were
atric brain tumors. As a group, they are poorly differentiated,
first identified in 2000 by Eberhart et  al. as a distinct type
highly cellular tumors with aggressive growth behaviors (Li
of supratentorial embryonal tumor. Ependymoblastoma, for-
et al., 2009). They include medulloblastomas and atypical tera-
merly classified as a distinct entity, has been reclassified as
toid rhabdoid tumors (ATRTs), which are discussed in detail
being within the category of ETMR. These tumors, which
in their own chapters, and an evolving group of tumors for-
also are known as embryonal tumors with abundant neuropil
merly classified as primitive neuroectodermal tumors (PNETs).
and true rosettes (ETANTRs), are rare CNS embryonal tumors
The PNET classification is being phased out; more recently
that typically arise in the cerebrum but are occasionally seen
these tumors have been reclassified as CNS embryonal tumors.
in the cerebellum and brainstem. They occur in very young
These other CNS embryonal tumors include embryonal tumors
children (Ryzhova et  al., 2011) and have a slightly higher
with multilayered rosettes (ETMRs), medulloepithelioma, CNS
predominance in girls than in boys (Gessi et  al., 2009). Neuro-
neuroblastoma, CNS ganglioneuroblastoma, and CNS embry-
imaging of an ETMR shows a large, well-delineated, solid mass
onal tumor Not Otherwise Specified (NOS). These types of
with heterogeneous contrast enhancement (Gessi et  al., 2009).
CNS embryonal tumors are rare, accounting for approximately
Some tumors demonstrate a cystic component (Figure 124-1).
3% of childhood brain tumors. Their rarity combined with
Their histologic characteristics are very distinctive and
their substantial heterogeneity has resulted in a poor under-
include focal high cellularity with abundant bands of neoplas-
standing of these tumors. However, classification of these
tic neuropil and the presence of both true rosettes and pseudo-
tumors is rapidly evolving based on molecular profiling studies,
rosettes (Louis et al., 2007) (Figure 124-2). These tumors are
and the mechanisms driving tumorigenesis of these CNS
distinguished by high-frequency focal amplification at chro-
embryonal tumors are just beginning to be recognized.
mosome locus 19q13.42 of the C19MC oncogenic microRNA
Historically, CNS embryonal tumors have been treated
cluster, often associated with high levels of expression of
with protocols used to treat medulloblastoma, perhaps a
LIN28 (Li et al., 2009; Ceccom et al., 2014). It has recently
by-product of these tumors’ similar histologic appearances.
been shown that C19MC amplification occurs as a fusion of
However, outcomes for patients with CNS embryonal tumors
C19MC with the promoter of TTYH1, a brain-specific gene
other than medulloblastomas have remained uniformly poor.
that encodes a chloride channel. The TTYH1 promoter is
This has led to the appreciation that these tumors respond
highly active, driving high levels of C19MC expression, which
poorly to medulloblastoma-based therapies and highlights
in turn activates DNMT3B, a DNA methyl transferase that
the need for a better definition of the clinical, histologic, and
modulates the cells to induce a state of dedifferentiation and,
genetic characteristics of these tumors to appropriately tailor
ultimately, tumorigenesis (Kleinman et al., 2014). Thus the
effective therapies for patients.
high-level amplicon activates a primitive developmental
mechanism as part of the oncogenic mechanism (Archer and
CLINICAL PRESENTATION Pomeroy, 2014).
The prognosis of ETMR is exceptionally poor, with median
CNS embryonal tumors generally involve the frontal, tempo-
survival of less than 1 year despite aggressive treatment.
ral, and parietal lobes, more so than the deep or posterior
fossa structures, and clinical manifestations are dependent on
the site of tumor origin. Most children present with nonspe-
cific complaints such as headache, nausea, vomiting, and
Medulloepithelioma
problems with balance, all of which are manifestations of The most common site of origin for medulloepitheliomas is
increased intracranial pressure (ICP). Complications of the periventricular region in the cerebrum. These tumors are
increased ICP include herniation, and care should be taken to typically quite large in size and may involve multiple lobes in
approach lumbar puncture with extreme caution (or avoid one or both cerebral hemispheres. They sometimes occur
completely) if an intracranial lesion is suspected. Other clini- intraventricularly and can be seen in sellar, infratentorial, and
cal manifestations of a supratentorial tumor might include spinal regions, and in the optic nerve.
motor deficits, alteration of consciousness, and seizures. Their histologic features include neural tube formation,
Deeper-seated tumors such as those involving the pineal including papillary, tubular, or trabecular arrangements of
region may present with Parinaud’s syndrome from compres- neoplastic neuroepithelium. These rare malignant tumors are
sion of the pretectal region. Tumors in the suprasellar region seen primarily in young children between the ages of 6 months
may result in visual disturbances and/or endocrine abnormali- and 5 years, and half occur in children less than 2 years old
ties. Posterior fossa tumors may present with ataxia, cranial (Louis et al., 2007). There is an equal distribution between
nerve deficits, and signs and symptoms of increased ICP. males and females.

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