Pathology of CNS: Eric M. Mirandilla MD, DPSP
Pathology of CNS: Eric M. Mirandilla MD, DPSP
Pathology of CNS: Eric M. Mirandilla MD, DPSP
• Myxopapillary
ependymomas are
distinct but related
lesions arising in the filum
terminale of the spinal
cord.
• Cuboidal cells, sometimes
with clear cytoplasm, are
arranged around papillary
cores; myxoid areas
contain neutral and acidic
mucopolysaccharides.
Related Paraventricular Mass Lesions
• Subependymomas
– are solid, sometimes calcified, slowgrowing nodules attached to
the ventricular lining and protruding into the ventricle; they are
usually asymptomatic butcan cause hydrocephalus.
• Choroid plexus papillomas
– recapitulate the normal choroid plexus; they exhibit connective
tissue papillae covered with a cuboidal-columnar ciliated
epithelium.
• Choroid plexus carcinomas are rare; they are typically
adenocarcinomas arising in children.
• Colloid cysts of the third ventricle are non-neoplastic lesions
of young adults; they are located at the foramina of Monro
and can result in noncommunicating hydrocephalus,
sometimes rapidly fatal
Neuronal Tumors
• Ganglioglioma is the most common CNS tumor of matureappearing
neurons (ganglion cells);
– it is slow growing, although the glial component can become frankly
anaplastic and the tumor more aggressive.
– One fifth of these tumors have activating BRAF mutations; most occur
in the temporal lobe and have a cystic component.
• Dysembryoplastic neuroepithelial tumor is a rare, low-grade
childhood neoplasm often presenting as a seizure disorder;
– prognosis after resection is good.
– Features include intracortical location, cystic changes, nodular growth,
“floating neurons” in a pool of mucopolysaccharide-rich fluid, and
surrounding neoplastic glia without anaplastic features.
• Central neurocytoma is a low-grade neuronal neoplasm within the
ventricles consisting of evenly spaced, round, uniform nuclei and
islands of neuropil.
Medulloblastomas
• account for 20% of childhood brain
tumors; they occur exclusively in
the cerebellum.
• Gross:
– Tumors are well circumscribed, gray,
and friable.
• Microscopic:
– Lesions are usually extremely
cellular, with sheets of anaplastic
cells exhibiting hyperchromatic
nuclei and abundant mitoses;
– cells have little cytoplasm and are
often devoid of specific markers of
differentiation, although glial and
neuronal features (e.g., Homer-
Wright rosettes) can occur.
– Extension into the subarachnoid
space can elicit prominent
desmoplasia.
Atypical Teratoid-Rhabdoid Tumor
• a highly malignant tumor of the posterior
fossa and supratentorium of young children;
survival is usually <1 year.
• Chromosome 22 deletions occur in >90%
• These are large, soft tumors that spread over
the brain surface;
– they are highly mitotic lesions histologically
characterized by rhabdoid cells, resembling those
seen in rhabdomyosarcoma.
Primary Central Nervous System
Lymphoma
• Primary CNS lymphoma accounts for 2% of extranodal
lymphomas and 1% of intracranial tumors;
– it is the most common CNS neoplasm in
immunocompromised hosts.
• Most primary brain lymphomas are of B-cell origin and
nearly all are latently infected by EBV;
– the most common histologic group is diffuse large-cell B-
cell lymphomas.
• These are aggressive tumors and respond poorly to
chemotherapy compared with their peripheral
counterparts.
Germ Cell Tumors
• Germ cell tumors occur along the midline in
adolescents and young adults; they constitute
0.2% to 1% of CNS tumors in European
populations but up to 10% of Japanese.
• Tumors most commonly occur in the pineal
(male predominance) and suprasellar regions.
• The histologic classification and therapeutic
responsiveness of CNS germ cell tumors
mirror those of their non-CNS counterparts
Pineal Parenchymal Tumors
• Pineal parenchymal tumors derive from
pineocytes; they range from well-
differentiated lesions with neuronal
differentiation (pineocytomas) to high-grade
tumors (pineoblastomas) that spread
throughout the CSF.
• High-grade pineal tumors tend to affect
children, whereas lower-grade lesions are
found more often in adults.
Meningiomas
• benign tumors of adults that arise from
arachnoid meningothelial cells and are
attached to the dura
• These are often associated with loss of
chromosome 22 (especially the long arm,
22q), leading to deletions of the NF2 gene
encoding the protein merlin, and associated
with greater chromosomal instability
Meningiomas
• Gross:
– Tumors are usually rounded
masses with well-defined dural
bases that compress
underlying brain but easily
separate from it;
• Microscopic:
– Several histologic patterns exist
(e.g., synctytial, fibroblastic,
transitional, psammomatous,
secretory, and microcystic) all
with approximately
comparable favorable
prognoses (WHO grade I/IV);
– among these, proliferation
index is the best predictor of
biologic behavior.
Meningiomas
• Anaplastic (malignant) meningiomas (WHO grade
III/IV) are aggressive tumors that resemble
sarcomas;
• mitotic rates are high (>20 per 10 high-powered
fields).
• Papillary meningiomas (pleomorphic cells
arranged around fibrovascular cores) and
rhabdoid meningiomas (sheets of cells with
hyaline eosinophilic cytoplasm composed of
intermediate filaments) also have a high
recurrence rate (WHO grade III/IV tumors).
Familial Tumor Syndromes
• Cowden syndrome: Dysplastic cerebellar
gangliocytomas due to PTEN mutation
• Li-Fraumeni syndrome: Medulloblastomas due
to p53 mutation
• Turcot syndrome: Medulloblastomas or
glioblastomas due to APC or mismatch repair
gene mutation
• Gorlin syndrome: Medulloblastomas due to
PTCH mutation
Tuberous Sclerosis Complex
• Tuberous sclerosis complex is an autosomal
dominant disorder occurring in 1 in 6000
births; it is characterized by autism, seizures,
and mental retardation
– leads to CNS hamartomas, including cortical
tubers (haphazardly arranged neurons and cells
expressing phenotypes intermediate between glia
and neurons) and subependymal hamartomas
(large astrocytic and neuronal clusters forming
subependymal giant cell astrocytomas).
von Hippel-Lindau Disease
• von Hippel-Lindau disease is an autosomal
dominant disorder; affected individuals
develop hemangioblastomas in the
cerebellum, retina, or brainstem and spinal
cord, as well as cysts involving the pancreas,
liver, and kidney.
• There is also a propensity for renal cell
carcinoma and pheochromocytomas
• END