Section XII. Neuro-oncology

XII.1.

Answer c.

For patients with HIV/AIDS, toxoplasmosis and CNS lym-

phoma are the top considerations for a mass lesion with

enhancing characteristics on brain MRI. Additional studies

would be helpful to distinguish between the two. Lesions,

such as the one pictured, that involve the corpus callosum

or the periventricular area and those larger than 4 cm are

more suggestive of CNS lymphoma than toxoplasmosis.

XII.2. Answer e.

Patients who have had prior brain radiation are at higher

risk for meningioma and astrocytoma.

XII.3. Answer d.

The MRI shows an enhancing lesion in the cerebello-

pontine angle, consistent with an acoustic neuroma.

Craniopharyngioma and dysembryoplastic neuroepithelial

tumors are not typically located in this site. Both meningi-

oma and acoustic neuroma can occur in the cerebellopon-

tine angle. However, acoustic neuroma can be inherited in

an autosomal dominant manner in patients with neurofi-

bromatosis type 2.

XII.4. Answer a.

These astrocytomas are well-known manifestations of tuber-

ous sclerosis (TS), affecting up to 20% of TS patients. The

tumor is low grade and arises in the ventricles of the brain.

XII.5. Answer c.

Verocay bodies are associated with schwannomas and are

not a characteristic of glioblastoma. The other choices are

all seen in World Health Organization grade IV glioblasto-

mas and make up the mnemonic AMEN (nuclear atypia,

mitoses, endothelial proliferation, and necrosis).

XII.6. Answer d.

The oligodendroglioma codeletion is required for the diag-

nosis of oligodendroglioma, according to the World Health

Organization 2016 guidelines.

XII.7. Answer b.

Grossly, medulloblastoma often appears as soft but firm

pink to dark gray masses. Histologically, the most common

characteristics are small round blue cells with scant cyto-

plasm; dark nuclei with nuclear molding or wrapping; and

neuroblastic rosettes with fibrillary centers.

XII.8. Answer a.

Primary neoplasms of the choroid plexus include choroid

plexus papilloma (WHO grade I), atypical choroid plexus

papilloma (WHO grade II), and choroid plexus carcinoma

(WHO grade III). Papillomas occur 5 times more often than

carcinomas.

XII.9. Answer c.

Complete central nervous system (CNS) staging is manda-

tory in all cases of CNS germ cell tumors because they have

a predilection for CSF dissemination to all levels of the

neuraxis, even at early disease stages. CNS staging should

include MRI of the head and total spine with contrast

medium, CSF cytologic evaluation, measurement of AFP

and β-hCG levels in both serum and CSF, and laboratory

studies of pituitary or hypothalamic hormones, or both.

XII.10. Answer c.

The H3K27M mutation has recently been shown to have an

important prognostic significance in diffuse astrocytomas

of the spinal cord. It may one day be a target for treatment

because some histone deacetylase–related treatments are

currently under study. The other options are sometimes

tested and found to be mutated, but they are not estab-

lished as a marker of poor prognosis.

XII.11. Answer d.

Most myxopapillary ependymomas behave in an indolent

way, at times staying static in size for a prolonged period.

With the patient’s symptoms improved, surveillance scans

would be a rational next step, initially at a short interval

and increasing the interval with stable scans. A possible

alternative could be to consider radiation therapy, but the

role of chemotherapy is limited.

XII.12. Answer d.

This patient likely has an asymptomatic incidentally dis-

covered meningioma. Metastasis is possible but would be

less likely with no clues (eg, edema) on imaging. In this

context, a period of surveillance MRI scans is commonly

recommended, and additional testing is deferred unless a

change is identified on a subsequent scan. A resection can

be considered, but at many centers it usually is reserved

for symptomatic or enlarging tumors. Radiation treatment

or chemotherapy would be difficult to recommend with-

out a pathologic diagnosis. If screening for malignancy is

pursued, then more extensive systemic imaging, looking

not only at the chest, should be recommended.

XII.13. Answer a.

The patient has neurofibromatosis type 2 (NF2) characterized

by bilateral acoustic neuromas. The gene for NF2 is located

on chromosome 22 and encodes for merlin. It is inherited in

an autosomal dominant manner. Neurofibromatosis type 1 is

inherited in an autosomal dominant manner and is located

on chromosome 17. Shagreen patches are seen in patients

with tuberous sclerosis.

XII.14. Answer c.

This patient has neurofibromatosis type 1 (NF1), an autoso-

mal dominant condition. Patients with NF1 may have café

au lait spots, iris Lisch nodules, optic glioma, and neurofi-

bromas. The neurofibromas are benign peripheral nerve

sheath tumors that have an infiltrative growth pattern

within the parent nerve and may have numerous axons.

They present as superficial dermal or subcutaneous nod-

ules. Neurofibromas can occur at any age, and they do not

have a sex predilection. Neurofibromatosis type 2 is associ-

ated with acoustic neuroma and is due to a mutation on

chromosome 22.

XII.15. Answer e.

Surgical excision of a solitary neurofibroma is considered

when the tumor is painful, the patient has associated neu-

rologic deficits, or the tumor shows increased growth. Use

of MEK inhibitors in the treatment of inoperable or refrac-

tory plexiform neurofibromas is evolving but is not first-

line therapy. A malignant peripheral nerve sheath tumor

(MPNST) may arise from a preexisting plexiform neurofi-

broma and can be aggressive, requiring surgical removal.

MPNSTs often are ≥5 cm and rapidly enlarge; they are

often associated with pain.

XII.16. Answer c.

It is important to know the frequency of these tumors and

to recall that lung cancer is the most common cancer and

thus also the most common to go to the brain, followed by

breast cancer. Melanoma is the third most common

because it tends to quickly metastasize to the brain, even

though it is not as frequent a cancer.

XII.17. Answer b.

Higher KPS scores are better. A KPS score ≥70 is consid-

ered functional. All the other features would be concern-

ing. Age ≤65 years is prognostically favorable; limited

systemic disease, smaller and fewer lesions, and absence

of leptomeningeal disease would all be more favorable.

XII.18. Answer d.

Breast cancer is most likely to, and is known to, progress

to leptomeningeal disease, resulting in additional compli-

cations in its treatment and prognosis.

XII.19. Answer b.

Radiation myelopathy can occur immediately after treat-

ment or take time to develop, even occurring years after

treatment. Acute encephalopathy occurs immediately after

treatment. Radiation necrosis is a subacute complication.

Radiation-induced dementia and peripheral nerve injuries

are more long-term complications.

XII.20. Answer d.

Intrathecal or intravenous methotrexate or high doses of

methotrexate can result in chemotherapy-induced leuko-

encephalopathy.

XII.21. Answer a.

Migraine attacks are not usually related to bevacizumab

treatment.

XII.22. Answer e.

Limbic encephalitis and FBDSs are common manifesta-

tions of LGI1 autoimmunity, which typically affects older

men and is often associated with hyponatremia. AQP4-IgG

is a biomarker for recurrent optic neuritis, transverse

myelitis (usually longitudinally extensive), and area pos-

trema (intractable nausea, vomiting, and hiccups). PCA-1

IgG is a biomarker for paraneoplastic cerebellar degenera-

tion, typically in women with gynecologic malignancies.

GAD65 antibodies are detected at high titer in patients with

stiff person syndrome, ataxia, and temporal lobe epilepsy.

VGCC-P/Q-type and VGCC-N-type are helpful in the diag-

nosis of Lambert-Eaton syndrome and cerebellar ataxia.

XII.23. Answer d.

Although encephalitis is encountered in patients with

multiple neural autoantibodies, the combination of ocular

findings (including retinopathy, optic neuropathy, and vit-

ritis), encephalomyelitis, and chorea are classic manifesta-

tions of CRMP-5 autoimmunity.

XII.24. Answer b.

PCA-1–immunoglobulin G is a biomarker of paraneoplas-

tic cerebellar degeneration, usually detected in patients

with ovarian or other Müllerian (gynecologic tract) adenocarcinoma and breast adenocarcinoma. Ovarian teratoma

is the most common neoplasm in patients with anti–N-

methyl-D-aspartate receptor encephalitis. Small cell lung

carcinoma is associated with multiple antibodies, includ-

ing antineuronal nuclear antibody 1 (ANNA-1) and γ-ami-

nobutyric acid antibody. Thyroid carcinoma and prostate

carcinoma are rarely associated with paraneoplastic neu-

rologic syndromes.