1. Answer D. (MN-100) Pilocytic astrocytomas are WHO grade I tumors that are potentially curable with gross total resection. However, a minority of patients develop recurrent tumors, so patients should be monitored periodically with serial MRI brain.

2. Answer C. (MN-100) Glioblastoma is the most common malignant primary brain tumor in adults. Meningiomas are the most common benign primary brain tumors. Brain metastases are the most common malignant brain tumors but are not primary tumors of the central nervous system.

3. Answer C. (MN-100) Maximal safe resection by an experienced brain tumor neurosurgeon. In centers with access to experienced brain tumor neurosurgeons, tumor resection is preferred over biopsy to avoid tissue undersampling (which could result in misdiagnosis) and the need for reoperation, given the therapeutic benefit of surgery in this disease. Stereotactic brain biopsy could be considered in situations where a more extensive resection is unsafe or there is high likelihood of an alternative diagnosis that would not benefit from resection (eg, tumefactive multiple sclerosis).

4. Answer E. (MN-100) The patient’s age, performance status, extent of gross resection, in addition to MGMT promotor methylation and IDH mutation status are all prognostic factors in the management of WHO grade IV glioblastoma.

5. Answer C. (MN-100) The H&E-stained section shows hypercellular brain with cells resembling oligodendrocytes with regular round nuclei and perinuclear halos. There is mild nuclear atypia. There are no mitoses, necrosis, or microvascular proliferation present, which would be indicative of a WHO grade III anaplastic oligodendroglioma.

6. Answer E. (MN-100) IDH-mutant gliomas harbor mutations in IDH1 or IDH2 that confer a neoenzymatic activity and result in the conversion of alpha-ketoglutarate (aKG) to 2-hydroxyglutarate (2HG) by mutant isocitrate dehydrogenase. 2HG inhibits aKG-dependent dioxygenases and multiple histone demethylases, resulting in widespread changes in DNA methylation and gene expression that are thought to culminate in gliomagenesis.

7. Answer D. (MN-100) The majority of oligodendrogliomas harbor mutations in IDH1 or IDH2, codeletion of chromosome arms 1p and 19q, and TERT promoter mutations.

8. Answer B. (MN-101) In the United States, WBRT is classically delivered to a total dose of 30 Gy in 10 fractions, although several other fractionation schedules have been shown to have similar rates of efficacy with no significant difference in toxicity (20 Gy in 5 fractions, 37.5 Gy in 15 fractions, etc.). However, short courses delivered in one to two fractions are associated with shorter progression-free survival and higher doses (>50 Gy) or hyperfractionation (increased number of fractions) is not associated with a survival benefit and is not utilized in clinical practice.

9. Answer B. (MN-101) This patient is diagnosed with limited (1-4) brain metastases at initial presentation of disease and can be managed with a variety of approaches. Of the given list, the most acceptable approach would be primary stereotactic radiosurgery to the intact brain metastases. Resection alone is associated with a high rate of local disease failure as well as distant intracranial failure based on level 1 evidence. Level 1 evidence also supports the use of primary stereotactic radiosurgery versus stereotactic radiosurgery and whole-brain radiation therapy for patients with limited brain metastases. Systemic therapy without intracranial penetration is not recommended as first-line treatment for a patient presenting with brain metastases without actionable mutation.

10. Answer A. (MN-101) This clinical vignette presents a case of a metachronous intracranial metastasis in a patient with a history of breast cancer. Given the size and symptomatic nature of her disease, there are many therapeutic strategies to provide local disease control while minimizing morbidity. Options include resection followed by stereotactic radiosurgery or hippocampal-avoidance whole-brain radiation therapy or use of stereotactic radiosurgery alone. Given the size of the lesion and symptomatic nature of the disease, conventional whole-brain radiation therapy would likely provide less benefit with regards to symptoms from direct mass effect and would be associated with a significant risk of neurocognitive decline.

11. Answer C. (MN-101) Systemic therapy traditionally had a limited role in the management of patients with brain metastases; however, the development of targeted therapies with intracranial penetration has led to a revitalization of the role of systemic therapy in patients with brain metastasis. Patients with EGFR mutations have multiple therapeutic options with high rates of intracranial efficacy. Presence of ALK rearrangement (as opposed to an absence) and treatment with ALK inhibitors are also associated with favorable intracranial response rates. HER-2/neu overexpression is observed in patients with breast cancer, for which targeted agents have been tested alone or in combination with radiotherapy. Although presence of a KRAS mutation is observed in patients with non–small cell lung cancer, this mutation is currently not associated with targetable agents that provide intracranial disease control.

12. Answer A. (MN-101) In patients with spinal cord compression from metastases from a solid tumor, resection is the primary modality for providing immediate decompression. There is level 1 evidence that the addition of surgery to radiation therapy in the setting of spinal cord compression was associated with improved neurologic outcomes as well as improved functional outcomes, such as ambulation and continence. Moreover, surgery was associated with decreased steroid and narcotic requirements. Furthermore, there was an associated survival benefit to resection in these patients.

13. Answer D. (MN-102) The most common genetic alteration in a sporadic meningioma (one occurring outside of a genetic predisposition syndrome) is NF2 deficiency. This may occur as an inactivating point mutation or as chromosome 22 loss. The exact pathophysiology of how NF2 deficiency leads to a meningioma is unknown. Similarly, there is no available approved drug that is known to target this mutation for treatment purposes. Other choices include additional genetic alterations that have been identified in subsets of meningioma but much less common. AKT and SMO mutations were of particular interest because drugs to target them are either approved or under investigation for different diagnoses. However, these are quite uncommon and even less common in those who require additional therapy.

14. Answer A. (MN-102) The typical MRI appearance of a meningioma is a homogenously enhancing extra-axial mass on T1-weighted postcontrast images. The other answers are incorrect. A peripherally enhancing mass with central necrosis is typical of a different brain tumor, a glioblastoma, which is a very malignant cancer. Occasionally, very aggressive treatment-refractory high-grade meningiomas can exhibit areas of central necrosis, but this is not common. A thin crescent-shaped mass just under the cortical surface describes the typical radiographic appearance of primary central nervous system lymphoma, which has a similar homogenous enhancement as meningioma but differs in location. Lymphoma is more likely periventricular, but usually intra-axial, whereas a meningiomas are nearly always extra-axial. A “whorl” is not a radiologic term but instead is a cellular histologic pattern seen in meningiomas.

15. Answer C. (MN-102) In this vignette, the most appropriate next step is observation with a repeat scan in 3 to 6 months to assess stability. The meningioma that was found is clearly asymptomatic. One can hypothesize that she has a hormonally sensitive meningioma, and having had four children may have contributed to the growth. An important part of her treatment plan would be counseling on further pregnancy. Without evidence of growth right now, most neuro-oncologists would not recommend any of the other choices.

16. Answer B. (MN-102) In this vignette, the patient is presenting with what clinically sounds like an ocular migraine. An incidental lesion is found on MRI, which has all the typical characteristics of a tiny presumed meningioma. In this scenario, a small, incidental, asymptomatic meningioma would be followed with surveillance imaging. Surgery would be reserved for larger, symptomatic, or growing meningiomas. Similarly, radiation would be an option if treatment was needed, but the patient was not appropriate for surgery or the tumor was in a surgically inaccessible location. Chemotherapy is typically only given in cases of a surgery and radiation refractory meningioma, which this is clearly not. Repeat MRI may be appropriate as part of observation; however, given the very low suspicion at this juncture for a rapidly growing malignancy, this would not be appropriate to perform in only 2 weeks.

17. Answer B. (MN-102) This is one of the most controversial and challenging situations in meningioma management, the patient with a gross totally resected atypical meningioma. For patients who have a WHO grade I meningioma and undergo surgical resection, they are usually managed with observation afterward irrespective of the extent of resection except in certain circumstances (ie, symptomatic residual disease). Patients with a WHO grade II meningioma that is subtotally resected or a WHO grade III meningioma of any extent of resection are all typically managed by following surgery with radiation to the residual disease and/or tumor bed. However, for the gross totally resected WHO grade II meningioma, the postoperative management is controversial and according to current standards and NCCN guidelines, either observation or radiation is an acceptable option. Multiple retrospective case series have reported an improvement in progression-free survival with radiation, yet other retrospective series have refuted that finding. No study has yet demonstrated an overall survival advantage with postoperative radiation. Currently there is an ongoing international randomized trial to try to answer this question. Chemotherapy is not appropriate for a patient with an initial presentation of grade II meningioma.

18. Answer B. (MN-102) In this particular setting, where there are multiple masses with edema in the patient with a known history of breast cancer, the most likely diagnosis is that these are dural metastases. If the edema was not present and there was an isolated single small dural-based lesion, maybe meningioma would still be a high probability. However, the fact that there are multiple masses with edema makes you suspect a more aggressive etiology. Given her known breast cancer, this makes metastatic disease the most likely answer, even though all the choices represent possible etiologies.

19. Answer E. (MN-102) This patient is presenting with a surgery and radiation refractory meningioma needing treatment for recurrence, so observation would not be appropriate unless the patient did not want any further therapy. In this circumstance, systemic therapy (ie, chemotherapy) is appropriate. The top choice would always be enrollment in a clinical trial, although that is not listed here. There is no FDA-approved therapy indicated for the treatment of meningioma; therefore, we turn to the NCCN guidelines to guide therapy choices. Sunitinib is a multiple tyrosine kinase inhibitor attractive for meningiomas because it targets both the VEGF and PDGF receptors. Other therapies in the guidelines include bevacizumab, bevacizumab + everolimus, interferon alpha, and somatostatin analogue therapy.

20. Answer B. (MN-103) The best next step is systemic workup including CT/PET body to rule out systemic involvement, which, if present, will require additional treatment of systemic lymphoma. Owing to its high sensitivity to chemotherapy, surgical resection is not considered standard of care in primary central nervous system lymphoma (PCNSL). High-dose methotrexate-based treatment is ideal once extent of disease evaluation workup has been completed and the diagnosis of PCNSL has been established. Steroids are useful for managing symptoms directly from tumor mass effect but are not the mainstay of long-term treatment and should generally be deferred until after the diagnosis is confirmed.

21. Answer B. (MN-103) Based on IESLG prognostic scoring, there are five risk factor components to the prognostication score: age >60 years, ECOG performance status score 2 to 4 (higher numbers indicating more functional dependence), deep brain involvement, serum LDH above normal, and CSF protein above normal. This patient has three of five negative risk factors (older age, deep location, and lack of functional independence). Two or three adverse risk factors correlate with 48% 2-year survival rate. Zero or one risk factor correlates with 2-year OS rate of 80%, and 4 or 5 factors with 15%.

22. Answer E. (MN-103) Leukoencephalopathy, hydrocephalus, and delayed neurotoxicity from whole-brain radiation is likely the cause of his clinical presentation. High-dose methotrexate itself can cause leukoencephalopathy, but this is increased with the addition of radiation. Recurrent PCNSL would likely lead to an acute presentation rather than a gradual slow decline. Infection would also present acutely with additional associated signs and symptoms.

23. Answer D. (MN-103) Comprehensive genomic analyses of PCNSL have revealed somatic mutations involving members of the NK-κB pathway, including frequent MYD88 mutations. The other mutations listed have been seen in gliomas.

24. Answer C. (MN-103) High-dose methotrexate-based chemotherapy is standard-of-care treatment for newly diagnosed PCNSL. Concurrent radiation and temozolomide is the standard-of-care treatment for newly diagnosed glioblastoma. Carboplatin and pemetrexed are used in treatment of non–small cell lung cancer. Whole-brain radiation is used for consolidation for PCNSL or for salvage therapy in PCNSL.

25. Answer B. (MN-104) Breast milk production in a nonpregnant patient suggests abnormally elevated prolactin levels, which should be confirmed in laboratory studies. Markedly elevated prolactin levels are associated with prolactin-secreting pituitary adenomas. These tumors respond well to dopamine agonists such as bromocriptine or cabergoline. If the tumor fails to respond by shrinking and normalizing prolactin levels, transsphenoidal resection of the tumor is the next best option.

26. Answer B. (MN-104) The symptoms are typical of hypothyroidism. In this scenario, this is due to the pituitary mass compressing the pituitary gland resulting in decreased secretion of cortisol, growth hormone, and thyroid-stimulating hormone (TSH).

27. Answer A. (MN-104) This patient may likely need surgical resection of his pituitary adenoma. Before undergoing surgery, an endocrinologic evaluation is necessary to determine his hormonal status and to make sure he does not have a markedly elevated prolactin level, which might best be treated with a dopamine agonist. Dopamine agonists are not administered empirically. There is no role for metastatic workup in this scenario unless he has known metastatic disease.