Comprehensive Review in Clinical Neurology: A Multiple Choice Question Book for the Wards and Boards

Chapter 8. Neuro-oncology

Question

Question 1

  1. A 5-year-old boy is brought in for evaluation of abnormal jerks and chaotic REM in all directions. He is also ataxic when attempting to walk and has sudden brief truncal and limb jerks. Which of the following is incorrect regarding this condition?

      a.  This paraneoplastic syndrome is most commonly associated with medulloblastoma

      b.  In adults, this condition may be associated with breast and small cell lung carcinoma

      c.  The neurologic manifestations respond to ACTH

      d.  Resection of the primary tumor will lead to resolution of this syndrome

      e.  In adults, it may be associated with Anti-Ri antibodies

Questions 2–3

  2. Which of the following is a variant of diffuse astrocytomas?

      a.  Gemistocytic

      b.  Protoplasmic

      c.  Pleomorphic xanthoastrocytoma

      d.  a and b

      e.  All of the above

  3. Which of the following is a variant of diffuse astrocytoma?

      a.  Pleomorphic xanthoastrocytoma

      b.  Subependymal giant cell astrocytoma

      c.  Pilocytic astrocytoma

      d.  Fibrillary astrocytoma

      e.  None of the above

  4. A 47-year-old woman with breast cancer presents with headache and multiple cranial neuropathies. Her MRI shows leptomeningeal enhancement, and CSF shows abnormal cells on cytologic examination. Which of the following is correct?

      a.  This patient has brain stem infiltration by the breast cancer causing multiple cranial neuropathies

      b.  CSF examination is very sensitive for this condition, with few false negatives

      c.  Some cases are treated with a combination of whole-brain radiation and intraventricular methotrexate

      d.  γ knife is the treatment of choice

      e.  Melanomas infiltrating the meninges have a better prognosis than lymphomas

  5. Which of the following risk factors is clearly associated with the development of gliomas?

      a.  Use of cell phones

      b.  Infections

      c.  Immunosuppression

      d.  Tobacco use

      e.  Radiation exposure

Questions 6–8

  6. A 60-year-old man with a history of headaches and recent personality change presents with altered mental status. An MRI of the brain is obtained and shown in Figure 8.1. Which of the following is the most likely diagnosis?

FIGURE 8.1 (A) Axial T1-weighted post-contrast MRI; (B) axial FLAIR MRI

      a.  Meningioma

      b.  Astrocytoma WHO grade II

      c.  Astrocytoma WHO grade IV

      d.  Ependymoma

      e.  Oligodendroglioma

  7. Which of the following histopathologic findings do you expect to find in a biopsy of the lesion shown in Figure 8.1?

      a.  Cells with “fried egg” appearance

      b.  Nuclear pseudopalisading

      c.  Perivascular pseudorosettes

      d.  Homer-Wright rosettes

      e.  Rosenthal fibers

  8. Which is the most likely survival time for the patient depicted in question 6?

      a.  15 years

      b.  10 years

      c.  5 years

      d.  3 years

      e.  15 months or less

  9. Which of the following tumors does not typically present with seizures?

      a.  Ganglioglioma

      b.  Dysembryoplastic neuroepithelial tumor

      c.  Oligodendroglioma

      d.  Ependymoma

      e.  Astrocytoma

10. A 49-year-old woman presents with 3 weeks of gradually progressive dysarthria, unsteadiness, and frequent falls. On examination she is found to have prominent nystagmus in all directions, with marked dysarthria. She also has truncal ataxia and dysmetria, which is more prominent in the upper than lower extremities. The patient has also been losing weight for the past 4 months. An MRI shows diffuse cerebellar atrophy, but no evidence of intracranial mass. Complete work-up detects a pelvic mass originating in the ovary. Which of the following is correct regarding this condition?

      a.  A leptomeningeal biopsy will certainly demonstrate an infiltrative neoplasm

      b.  CSF cytology and flow cytometry are very specific for the diagnosis of this condition

      c.  Anti-Tr antibodies are most likely to be positive in this patient

      d.  Anti-Hu antibodies are the most common cause of this condition especially in the setting of breast carcinomas

      e.  Anti-Yo antibodies are likely to be positive in this patient

11. A patient presents with an MRI that is shown in Figure 8.2, and the histopathology shows a glial neoplasm with necrosis and endothelial hyperplasia. What treatment options will be potentially beneficial?

FIGURE 8.2 Axial T1-weighted postcontrast MRI

      a.  Surgical resection

      b.  Radiation therapy

      c.  Temozolomide

      d.  a and c

      e.  a, b, and c

12. Regarding gliomas, which of the following is not a poor prognostic factor?

      a.  Older age

      b.  Mixed oligoastrocytoma as compared to pure astrocytic type

      c.  Ring enhancing with gadolinium

      d.  Poor performance status

      e.  Necrotic center with pseudopalisading nuclei

13. Which of the following paraneoplastic syndromes is associated with the wrong antibody and neoplasm?

      a.  Retinal degeneration—anti-recoverin—small cell lung carcinoma

      b.  Optic neuropathy—anti-Hu—breast cancer

      c.  Paraneoplastic sensory neuropathy—anti-Hu—small cell lung cancer

      d.  Sensory neuronopathy—anti-Hu—small cell lung cancer

      e.  Lambert-Eaton myasthenic syndrome—anti-voltage-gated calcium channel (P/Q type)—small cell lung cancer

14. A 59-year-old woman presents with headaches and is found to have a brain mass. A biopsy is obtained, which is shown in Figure 8.3. Which of the following is the most likely diagnosis?

FIGURE 8.3 Brain specimen (Courtesy of Dr. Richard A. Prayson). Shown also in color plates

      a.  Fibrillary astrocytoma

      b.  Oligodendroglioma

      c.  Glioblastoma

      d.  Meningioma

      e.  Ependymoma

15. Which of the following is correct regarding anaplastic astrocytoma?

      a.  It is a WHO grade II tumor

      b.  It is well circumscribed, with no infiltration seen microscopically

      c.  Median survival is 10 to 15 years

      d.  p53 mutations are seen in these type of tumors

      e.  1p19q deletion is common in this tumor and carries a better prognosis

16. A 5-year-old patient presents with 2 weeks of gradually worsening headaches, now with nausea and vomiting. An MRI is obtained, which is shown in Figure 8.4. Which is the most likely diagnosis?

FIGURE 8.4 Axial T1-weighted postcontrast MRI

      a.  Glioblastoma multiforme

      b.  Oligodendroglioma

      c.  Diffuse fibrillary astrocytoma

      d.  Pilocytic astrocytoma

      e.  Acoustic schwannoma

17. A 17-year-old boy with focal epilepsy undergoes surgical resection of a right temporal lobe lesion, and the biopsy is consistent with a pleomorphic xanthoastrocytoma. Which of the following is correct regarding this lesion?

      a.  It is a deeply seated and infiltrating lesion

      b.  Eosinophilic granular bodies are not typically seen

      c.  Intercellular reticulin deposition is common

      d.  Prognosis is generally poor with more than 50% undergoing malignant transformation

      e.  Can be seen in the temporal lobe, but is more common in the frontal lobes

18. A 12-year-old boy is found to have a subependymal giant cell astrocytoma. Which of the following is correct regarding this lesion?

      a.  It is commonly sporadic and rarely associated with tuberous sclerosis

      b.  It is infiltrative

      c.  The presence of “candle gutterings” suggests an alternative diagnosis

      d.  It is benign (WHO grade I)

      e.  Even though it can be seen in young patients, it is most commonly encountered in the elderly

19. Which of the following is incorrect regarding oligodendroglioma?

      a.  WHO grade II oligodendrogliomas are usually nonenhancing

      b.  They are usually found superficially and involve the cortex

      c.  They occur more frequently in the frontal lobes

      d.  Borders are ill-defined as the tumor is infiltrating

      e.  In the classic type of this tumor, glial fibrillary acidic protein is positive

20. A 7-year-old patient presents with a posterior fossa tumor. A biopsy is obtained, which is shown in Figure 8.5. Which is the most likely diagnosis?

FIGURE 8.5 Brain specimen (Courtesy of Dr. Richard A. Prayson). Shown also in color plates

      a.  Cerebellar hemangioblastoma

      b.  Pilocytic astrocytoma

      c.  Glioblastoma multiforme

      d.  Oligodendroglioma

      e.  Meningioma

21. A 42-year-old patient presents with a seizure and is found to have a brain mass. A biopsy is obtained, which is shown in Figure 8.6. Which of the following is the most likely diagnosis?

FIGURE 8.6 Brain specimen (Courtesy of Dr. Richard A. Prayson). Shown also in color plates

      a.  Pilocytic astrocytoma

      b.  Glioblastoma

      c.  Oligodendroglioma

      d.  Ependymoma

      e.  Hemangioblastoma

Questions 22–23

22. A 5-year-old boy presents with headaches, nausea, and vomiting. A posterior fossa tumor is found on imaging and a biopsy is obtained, shown in Figure 8.7. Which of the following is correct regarding this tumor?

FIGURE 8.7 Brain specimen (Courtesy of Dr. Richard A. Prayson). Shown also in color plates

      a.  In children, this tumor more commonly occurs in the spinal cord as compared to the intracranial region

      b.  When intracranial, this tumor is more commonly supratentorial than infratentorial

      c.  Homer-Wright rosettes are common in this type of tumor

      d.  It is highly infiltrative

      e.  Patients younger than 3 years of age have a worse prognosis

23. Which of the following is incorrect regarding this type of tumor?

      a.  There are perivascular pseudorosettes

      b.  The myxopapillary variant arises from the filum terminale

      c.  Surgical resection may be curative, and prognosis depends on the extent of resection

      d.  It may produce drop metastases

      e.  It may be associated with neurofibromatosis type 1 (NF1)

24. A patient with epilepsy is found to have an abnormality on an MRI of the brain. The biopsy was consistent with a diagnosis of ganglioglioma. Which of the following is correct regarding this abnormality?

      a.  These tumors are composed only of glia

      b.  These tumors are composed only of neurons

      c.  Eosinophilic granular bodies are commonly encountered

      d.  They are highly infiltrative

      e.  Treatment requires a combination of surgical resection, radiation, and chemotherapy

25. A 29-year-old man undergoes an MRI for evaluation of headaches. A lateral ventricular mass is found, and after surgical resection, the pathology is consistent with a neurocytoma. Which of the following is correct regarding this tumor?

      a.  Positive for synaptophysin

      b.  Highly infiltrative tumor

      c.  WHO grade III

      d.  Most commonly located in the fourth ventricle

      e.  Glial fibrillary acidic protein positive

Questions 26–27

26. A 50-year-old man presents with a seizure and is found to have an intracranial tumor on MRI, which is shown in Figure 8.8. Which of the following is correct?

FIGURE 8.8 Axial T1-weighted postcontrast MRI

      a.  This tumor arises from glia

      b.  The origin is glioneuronal

      c.  This tumor originates from arachnoid cap cells

      d.  This is a metastatic tumor

      e.  This tumor frequently infiltrates the brain parenchyma

27. Which of the following is correct regarding this tumor?

      a.  This tumor is more common in men

      b.  It may be associated with neurofibromatosis type 2

      c.  These are rapidly growing, infiltrative tumors

      d.  A dural tail on MRI is not likely to be seen with these type of tumors

      e.  Previous radiation is not associated with this type of tumor

28. A 29-year-old man undergoes surgical resection of a cerebellar mass. The histopathologic specimen is shown in Figure 8.9. Which of the following is correct?

FIGURE 8.9 Brain specimen (Courtesy of Dr. Richard A. Prayson). Shown also in color plates

      a.  The MRI of this type of lesion shows a cyst with an enhancing mural nodule

      b.  Is a highly infiltrative lesion

      c.  This tumor is classified as WHO grade III

      d.  Is more common in children

      e.  More than 90% of the cases are associated with von Hippel-Lindau

29. A biopsy of a cerebellar mass is obtained from a 7-year-old patient, shown in Figure 8.10. Which of the following is the most likely diagnosis?

FIGURE 8.10 Brain specimen (Courtesy of Dr. Richard A. Prayson). Shown also in color plates

      a.  Medulloblastoma

      b.  Oligodendroglioma

      c.  Pilocytic astrocytoma

      d.  Meningioma

      e.  Glioblastoma

30. Which of the following is correct regarding pineal tumors?

      a.  Pineocytomas are more common in children

      b.  Pineoblastomas are more common in the elderly

      c.  Pineoblastomas may spread via the craniospinal axis or metastasize

      d.  Pineoblastoma cells may resemble mature pineocytes

      e.  Pineocytomas have very high mitotic activity

31. Which of the following options is incorrect regarding the various types of cysts that can be found in the CNS?

      a.  Colloid cysts can be associated with acute hydrocephalus and sudden death

      b.  Dermoid cysts contain hair follicles, sebaceous glands, and sweat glands

      c.  Epidermoid cysts are most commonly located in the cerebellopontine angle

      d.  An MRI of epidermoid cysts shows hyperintensity on T1 and T2 with no restriction on DWI

      e.  Arachnoid cysts are lined by arachnoid cap cells

32. Which of the following is incorrect regarding medulloblastoma?

      a.  It is associated with genetic defects in chromosome 17

      b.  It originates from pluripotential cells

      c.  N-myc amplification is associated with poorer prognosis

      d.  Patients with younger age at diagnosis have better prognosis

      e.  It is more common in males

33. A 9-year-old boy with intractable epilepsy undergoes temporal lobectomy. The histopathologic specimen is shown in Figure 8.11. Which of the following is incorrect regarding this tumor?

FIGURE 8.11 Brain specimen (Courtesy of Dr. Richard A. Prayson). Shown also in color plates

      a.  Most common location is the temporal lobe

      b.  This lesion often has a cortical or juxtacortical location

      c.  Floating neurons are characteristic of this lesion

      d.  It is a WHO grade I tumor

      e.  On MRI, it has a heterogeneous contrast-enhancing pattern

Questions 34–35

34. A 35-year-old man with HIV presents with headaches and altered mental status, and is found to have an intracranial mass. A biopsy is obtained, which is shown in Figure 8.12. Which of the following is the most likely diagnosis?

FIGURE 8.12 Brain specimen (Courtesy of Dr. Richard A. Prayson). Shown also in color plates

      a.  Glioblastoma

      b.  Lymphoma

      c.  Oligodendroglioma

      d.  Meningioma

      e.  Ependymoma

35. Which of the following is incorrect regarding this condition?

      a.  It is most commonly a diffuse, large B-cell tumor

      b.  Primary tumors of this type usually involve the parenchyma rather than the leptomeninges

      c.  Steroid use should be avoided prior to biopsy if this neoplasm is suspected

      d.  It is associated with Epstein-Barr virus, especially in immunocompromised patients

      e.  Surgical resection is the cornerstone of treatment

36. A 12-year-old boy with a bitemporal hemianopia is found to have a suprasellar mass. The lesion is resected, and a biopsy specimen is shown in Figure 8.13. Which of the following is incorrect regarding this tumor?

FIGURE 8.13 Suprasellar mass specimen (Courtesy of Dr. Richard A. Prayson). Shown also in color plates

      a.  It can be associated with diabetes insipidus

      b.  It is seen only in children

      c.  The cysts contain material that resembles machine-oil fluid

      d.  The fluid in the cysts may elicit a xanthogranulomatous inflammatory process

      e.  It originates from remnants of Rathke’s pouch

37. A 4-year-old boy is found to have an intraventricular mass, which is biopsied. The histopathologic specimen is shown in Figure 8.14. Which of the following is incorrect regarding this lesion?

FIGURE 8.14 Intraventricular mass specimen (Courtesy of Dr. Richard A. Prayson). Shown also in color plates

      a.  Most common location is in the lateral ventricles

      b.  CSF production may be increased

      c.  It may present with hydrocephalus and features of increased intracranial pressure

      d.  It is a WHO grade II tumor

      e.  It is more common in children

38. A 41-year-old man presents with multiple cranial neuropathies. An intracranial tumor is found compressing the brain stem, and given the radiologic appearance, there is suspicion for a chordoma. Which of the following is incorrect regarding this tumor?

      a.  The clivus and sacrococcygeal regions are the most common locations

      b.  It originates from the notochord

      c.  It is infiltrative and lobulated

      d.  It consists of physaliphorous cells

      e.  It invades nervous tissue but spares the bone

39. A 36-year-old woman presents with gradually progressive unsteadiness and hearing loss in the left ear. An MRI is obtained, which is shown in Figure 8.15. Which of the following is the most likely diagnosis?

FIGURE 8.15 (A) Axial T1-weighted postcontrast MRI; (B) axial FLAIR MRI

      a.  Vestibular schwannoma

      b.  Oligodendroglioma

      c.  Cerebellar hemangioblastoma

      d.  Ependymoma

      e.  Metastatic lesion

Questions 40–41

40. Which of the following is the order of frequency from most common to least common origin of brain metastases:

      a.  Lung, melanoma, prostate, breast

      b.  Lung, breast, melanoma, colon

      c.  Breast, lung, melanoma, kidney

      d.  Lung, melanoma, thyroid, breast

      e.  Colon, breast, lung, melanoma

41. Which of the following is incorrect regarding brain metastases?

      a.  They are more common than primary brain tumors

      b.  Hemorrhagic metastasis can be seen with melanomas, non–small cell carcinomas, and renal cell carcinomas

      c.  The majority are infratentorial

      d.  Multiple metastatic lesions can be seen with small cell carcinomas and melanomas

      e.  Steroids are used to treat surrounding edema in brain metastasis

42. A histopathologic specimen from a pontocerebellar mass is shown in Figure 8.16. Which of the following is correct regarding this tumor?

FIGURE 8.16 Pontocerebellar mass specimen (Courtesy of Dr. Richard A. Prayson). Shown also in color plates

      a.  Most common location is the facial nerve

      b.  Antoni A pattern has a loose appearance

      c.  Verocay bodies are seen in this picture and are characterized by a palisading arrangement of the cells

      d.  This is a malignant tumor, categorized as WHO grade III

      e.  This tumor is diffusely infiltrating

43. A 72-year-old man with diabetes is undergoing visual assessment for renewal of his driver’s license and he fails the vision examination. On evaluation by his ophthalmologist he is found to have bitemporal hemianopia. An MRI of the brain is done, which is shown in Figure 8.17; the lesion measures 1.9 by 1.3 by 2.3 cm. The mass is resected, and pathological analysis reveals the findings shown in Figure 8.18. What is the most likely diagnosis in this patient?

FIGURE 8.17 (A) Coronal T1-weighted pre-contrast MRI; (B) Coronal T1-weighted post-contrast MRI; (C) Sagittal T1-weighted pre-contrast MRI; (D) Sagittal T1-weighted post-contrast MRI.

      a.  Craniopharyngioma

      b.  Pituitary microadenoma

      c.  Pituitary macroadenoma

      d.  Rathke’s cleft cyst

      e.  Pituitary apoplexy

44. A patient presents with a seizure, and the MRI obtained is shown in Figure 8.19. Which of the following is the most likely diagnosis?

      f.  Metastasis

      g.  Meningioma

      h.  Low-grade diffuse fibrillary astrocytoma

      i.  Glioblastoma

      j.  Ependymoma

45. An infiltrative brain lesion is biopsied and immunohistochemical analysis is obtained. It is glial fibrillary acidic protein positive, cytokeratin is negative, Melan-A is negative, CD45 is negative, CD20 is negative, and Ki-67 is found in a very high percentage. Which of the following is the most likely diagnosis?

      a.  Astrocytoma

      b.  Carcinoma

      c.  Melanoma

      d.  Lymphoma

      e.  Gliosis

46. Which of the following is incorrect regarding astrocytomas?

      a.  They originate from neuroglia

      b.  Pilocytic astrocytoma is a WHO grade II tumor

FIGURE 8.18 Pituitary mass specimen (Courtesy of Dr. Richard A. Prayson). Shown also in color plates

FIGURE 8.19 (B) Axial FLAIR MRI; (A) axial T1-weighted post-contrast MRI

      a.  Anaplastic astrocytoma is a WHO grade III tumor

      b.  Glioblastoma is a WHO grade IV tumor

      c.  Seizure is a common presentation

47. A 21-year-old man presented initially with depression 3 months ago, treatment was started, however, since then the patient has significant personality changes, with visual hallucinations and confusion. He also has prominent anterograde amnesia. The progression has been very gradual. His MRI and PET scan are shown in Figure 8.20. Which of the following is incorrect regarding this syndrome?

FIGURE 8.20 (A) Axial FLAIR MRI; (B) FDG-PET scan. Shown also in color plates

      a.  This patient has limbic encephalitis

      b.  This patient most likely has a testicular mass with anti-Hu antibodies in the serum

      c.  Seizures may occur

      d.  Can occur in older patients, in which case it is associated with small cell lung cancer and ANNA-1 antibodies

      e.  The testicular tumor most often associated with this syndrome is a germ cell tumor

48. Regarding the prognosis of oligodendrogliomas, which of the following is correct?

      a.  Chromosome 1p and 19q deletions confer a worse prognosis

      b.  Younger patients have better survival

      c.  p16 gene deletion is associated with better outcomes

      d.  p53 mutations occur in more than 50% of the cases

      e.  The prognosis in oligodendrogliomas is worse than in astrocytomas

49. A 52-year-old man presents with headaches and is diagnosed with a glioblastoma multiforme of the right frontal lobe. He is offered treatment with surgery, radiation, and chemotherapy, but decides not to be treated at all, except with medications that might symptomatically help his headache. He states to his neuro-oncologist that he understands that lack of any treatment could shorten his survival by several months, but says he would rather spend what time he has left traveling with his family and seeing friends. His family supports his decision. The neuro-oncologist feels that the patient could gain a few months with relatively good quality of life with the right treatment plan, and is surprised at the patient’s decision. Which of the following statements would be an appropriate reaction from the neuro-oncologist on the basis of the principle of autonomy?

      a.  “I would like to obtain a psychiatric evaluation because I don’t think you understand the implications of your decision and I want to get a court-order to treat you with surgery, radiation, and chemotherapy”

      b.  “It’s a free world, if you don’t want therapy that’s fine, but if you’re not going to listen to my opinion, then I can’t give you prescriptions for corticosteroids or any other treatment for your headaches, maybe you should see your primary doctor about that”

      c.  “I respect your decision, even though I feel there are some benefits of therapy, and therapy will always be an option for you if you change your mind down the line. There are some options to treat your headache that I will prescribe to you”

      d.  “You are in denial right now, you clearly don’t understand the implications of your decisions, let’s talk about this again in a few days, I’m sure you’ll change your mind, you’d be crazy not to”

      e.  “I wouldn’t be recommending all these treatment options if I wasn’t sure that’s the best thing for you, this is my area of expertise, and I think you should strongly re-consider, and take the treatment I am offering”

Answer Key

1. a

2. d

3. d

4. c

5. e

6. c

7. b

8. e

9. d

10. e

11. e

12. b

13. b

14. c

15. d

16. d

17. c

18. d

19. e

20. b

21. c

22. e

23. e

24. c

25. a

26. c

27. b

28. a

29. a

30. c

31. d

32. d

33. e

34. b

35. e

36. b

37. d

38. e

39. a

40. b

41. c

42. c

43. c

44. a

45. a

46. b

47. b

48. b

49. c

Answers

 1. a

This patient has opsoclonus myoclonus syndrome. This syndrome can present in adults with breast, ovarian, and small cell lung cancer, as well as in children with neuroblastoma (not medulloblastoma).

Clinically, these patients have spontaneous rapid, irregular, and high-amplitude conjugate eye movements that occur in any direction, as well as diffuse myoclonic jerks, and frequent ataxia.

CSF may be normal or show a mild pleocytosis, and MRI is typically normal.

Anti-Ri (also known as ANNA-2) antibodies are seen in this syndrome and especially associated with breast cancer, but can also be seen in a small percentage of small cell lung cancer. Anti-Hu (or ANNA-1) antibodies have been reported in adults with small cell lung cancer and children with neuroblastoma. There is no specific neuropathologic finding.

Characteristically, children with neuroblastoma respond to treatment with ACTH, and may have resolution of the neurologic manifestations when the neuroblastoma is treated. The prognosis is worse in adults.

 Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology, 9th ed. New York: McGraw-Hill; 2009.

 2. d, 3. d

Diffuse astrocytomas can be classified according to the histopathologic cell type into fibrillary, gemistocytic, and protoplasmic. Diffuse astrocytomas are infiltrating neoplasms, categorized as WHO grade II. These are slow-growing tumors that may evolve to an anaplastic astrocytoma or glioblastoma. In general, the MRI shows a T2-hyperintense lesion with no enhancement with gadolinium.

Fibrillary astrocytomas are prototypical and more common, with elongated hyperchromatic nuclei, scant cytoplasm, and the presence of a fibrillary background. Gemistocytic astrocytomas are characterized by a round prominent eosinophilic cytoplasm. Protoplasmic astrocytomas are composed of cells with oval-shaped nuclei with scant cytoplasm and a microcystic background.

Pleomorphic xanthoastrocytoma is not a diffuse astrocytoma and is rather a different type of astrocytoma, which is localized superficially, more commonly in the temporal lobe, with well-demarcated borders, and frequently associated with seizures.

Subependymal giant cell astrocytoma and pilocytic astrocytomas are also well-circumscribed neoplasms and not categorized under the diffuse astrocytomas.

 Prayson RA, Goldblum JR. Neuropathology, 1st ed. Philadelphia, PA: Elsevier; 2005.

 Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology, 9th ed. New York: McGraw-Hill; 2009.

 4. c

This patient has meningeal carcinomatosis, and these cases are sometimes treated with whole-brain radiation plus intraventricular methotrexate.

Certain cancers can spread to the meninges producing a carcinomatous meningitis. This can be seen with adenocarcinoma of the breast, lung and gastrointestinal tract, melanoma, childhood leukemia, and systemic lymphoma. Prostate cancer has been described to spread to the leptomeninges, and this is thought to occur through dissemination via the Batson’s plexus, which is a network of valveless veins that connect pelvic veins with internal vertebral veins.

The clinical manifestations of leptomeningeal disease are varied, but frequently, these patients present with headache and backache. Polyradiculopathies, multiple cranial neuropathies, and altered mental status are frequently seen. Some patients have features of increased intracranial pressure and hydrocephalus. The MRI shows leptomeningeal enhancement. The diagnosis can be established with CSF studies using cytologic evaluation and flow cytometry. CSF also will show a pleocytosis with increased protein and sometimes reduced glucose. However, CSF cytologic analysis is not sensitive, and many times repeated testing may be needed. In some cases, leptomeningeal biopsy may be required.

The treatment consists of radiation therapy to symptomatic areas, sometimes requiring whole-brain radiation. Some cases are treated with intrathecal chemotherapy and, preferably, intraventricular chemotherapy with methotrexate via an Ommaya reservoir. Unfortunately, the combination of brain radiation and chemotherapy carries a significant risk of leukoencephalopathy. Patients with meningeal carcinomatosis have a poor prognosis, usually with survivals of less than 6 months. In general, best response occurs in lymphomas, breast cancer, and small cell lung cancers. Worse prognosis is seen with other types of lung cancer and melanomas.

In this case, the leptomeningeal disease explains the multiple cranial neuropathies, and there is no indication to think about a brain stem infiltrative disease.

γ knife targets focal lesions, and is not useful in diffuse meningeal disease.

 Cone LA, Koochek K, Henager HA, et al. Leptomeningeal carcinomatosis in a patient with metastatic prostate cancer: Case report and literature review. Surg Neurol. 2006; 65:372–376.

 Prayson RA, Goldblum JR. Neuropathology, 1st ed. Philadelphia, PA: Elsevier; 2005.

 Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology, 9th ed. New York: McGraw-Hill; 2009.

 5. e

Radiation exposure is a well-established risk factor known to be associated with the development of gliomas. Radiation for previous neoplasia of the CNS may increase the risk of developing a glioma, frequently a malignant one.

Gliomas are the most common primary brain tumor, and incidence increases with age. There are no other clearly associated risk factors. There is no clear link between these tumors and cell phone use. Immunosuppression and tobacco use have not been associated with these neoplasms.

 Rowland LP, Pedley TA. Merritt’s Neurology, 12th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2010.

 6. c

This patient has an astrocytoma WHO grade IV, or glioblastoma. The MRI demonstrates a neoplasm crossing the corpus callosum, with strong gadolinium enhancement. There are hypointense areas that may correlate with necrosis, and there is also significant edema as seen on the FLAIR image. The typical tumor that crosses the corpus callosum is glioblastoma, and this appearance is called a “butterfly lesion.” Lymphomas have also been reported to cross the corpus callosum; however, this is less common.

Glioblastoma is the most common primary brain tumor, accounting for close to 50% of all gliomas. They typically present in adult patients usually above 50 years of age, manifesting with focal neurologic deficits, headaches, and other features of increased intracranial pressure and seizures.

Meningioma is an extra-axial tumor that arises from the meninges rather than from within the brain parenchyma, though orbitofrontal and falcine meningiomas can often present with symptoms related to frontal lobe dysfunction. The MRI shown in Figure 8.1 clearly demonstrates an intra-axial tumor, within the brain parenchyma, which is not consistent with meningiomas.

Astrocytoma WHO grade II typically shows T2 hyperintensity, but no contrast enhancement. Ependymomas originate from the ependyma and are typically localized in the ventricles. Oligodendrogliomas are hemispheric masses usually arising superficially and with cortical involvement.

 Prayson RA, Goldblum JR. Neuropathology, 1st ed. Philadelphia, PA: Elsevier; 2005.

 Rowland LP, Pedley TA. Merritt’s Neurology, 12th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2010.

 7. b

The patient depicted in question 6 has a glioblastoma, in which nuclear pseudopalisading, or arrangement of nuclei in a palisading pattern around areas of necrosis, can be found. Glioblastoma (astrocytoma WHO grade IV) is the most common primary brain tumor, and is a highly infiltrating and invasive tumor. Other histopathologic features of glioblastoma include nuclear atypia, mitoses, endothelial hyperplasia, and necrosis.

Cells with “fried egg” appearance are seen in oligodendrogliomas. Perivascular pseudorosettes are seen in ependymomas, and Homer-Wright rosettes are seen in medulloblastoma. Rosenthal fibers can be seen in Alexander’s disease, pilocytic astrocytoma, pleomorphic xanthoastrocytoma, and chronic reactive gliosis.

 Prayson RA, Goldblum JR. Neuropathology, 1st ed. Philadelphia, PA: Elsevier; 2005.

 Rowland LP, Pedley TA. Merritt’s Neurology, 12th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2010.

 8. e

This patient most likely has a survival time of about 15 months or less. Patients with astrocytomas will have different prognoses depending on the histologic grade, being approximately 5 to 10 years for grade II, 2 to 3 years for grade III, and 1 year or less for grade IV.

The prognosis depends on other factors as well. Age is a very important factor, and younger patients do better than older ones. Performance status is also very important, and patients with poor baseline condition and significant neurologic deficits have a worse prognosis.

 Prayson RA, Goldblum JR. Neuropathology, 1st ed. Philadelphia, PA: Elsevier; 2005.

 Rowland LP, Pedley TA. Merritt’s Neurology, 12th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2010.

 9. d

Ependymoma does not typically present with seizures. This type of tumor is the third most common CNS tumor in children, and 90% occur intracranially, most commonly in the infratentorial region, typically in the fourth ventricle. Given the location, these tumors tend to obstruct CSF flow, and features of increased intracranial pressure and hydrocephalus are the most common manifestations. Ependymomas in the supratentorial region occur in the periventricular region, but they may uncommonly be more superficial. Ependymomas can also occur in the spinal cord, more commonly in adults.

Ganglioglioma, dysembryoplastic neuroepithelial tumors, oligodendrogliomas, and astrocytomas frequently present with seizures.

 Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008.

 Prayson RA, Goldblum JR. Neuropathology, 1st ed. Philadelphia, PA: Elsevier; 2005.

10. e

This patient has a paraneoplastic syndrome consistent with paraneoplastic cerebellar degeneration. It has a prominent association with ovarian and breast carcinoma, but can also be seen in Hodgkin’s lymphoma, small cell carcinoma of the lung, and other visceral tumors.

The patient presents with cerebellar symptoms with a subacute, gradual course over a period of weeks to months. Typically, patients have ataxia that affects the trunk and limbs. They also have nystagmus and prominent dysarthria. Other neurologic manifestations may occur, including diplopia, vertigo, and sensorineural hearing loss.

CSF studies may be completely normal but in some cases, may show slight increase in the white cell count and protein. CT and MRI may be normal at the onset, but there may be evidence of increased signal in the cerebellar white matter and eventually atrophy of the cerebellum. Pathologically, there are diffuse degenerative changes of the cerebellar cortex and deep nuclei, and loss of Purkinje cells.

Anti-Yo antibodies (also known as anti–Purkinje cell antibodies) are seen in the serum of about 50% of patients with this syndrome, especially in those with ovarian cancer, but in smaller percentages of patients with breast carcinoma. Some patients may have anti-Hu antibody (also known as ANNA-1), especially in the setting of small cell carcinoma of the lung. Anti-Tr antibody is associated with lymphomas.

In many cases, the paraneoplastic syndrome develops in a patient with advanced malignancy; however, in some patients the paraneoplastic neurologic manifestations precede the malignancy and ongoing work-up for malignancy is required.

There is little evidence to guide therapy of paraneoplastic cerebellar degeneration. The progression may subside with removal of the underlying neoplasm, if possible, and there have been reports of some improvement with plasmapheresis, intravenous corticosteroids, and intravenous immunoglobulin, though the prognosis is generally poor.

 Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology, 9th ed. New York: McGraw-Hill; 2009.

11. e

Surgical resection, radiation therapy, and chemotherapy with temozolomide are potentially beneficial for patients with glioblastoma, the most likely tumor type in this patient, based on the imaging and histopathologic findings.

Complete removal of the tumor is not possible given that astrocytomas (especially glioblastoma) are infiltrating tumors with no clear margins. However, if the tumor characteristics permit, surgery with near-complete resection or debulking improves neurologic function, reduces mass effect, and prolongs survival. Unfortunately, this may not be possible with very large tumors or with those crossing the corpus callosum.

Radiotherapy with focal radiation is an important treatment option, and it is given with a target total dose of 60 Gy for high-grade gliomas, divided in several fractions over 6 to 7 weeks.

Adjuvant chemotherapy has been shown to prolong survival in meta-analyses in which older nitrosourea agents such as carmustine were used. Temozolomide is an alkylating agent that has replaced nitrosoureas and is currently widely used as an adjuvant therapy. The addition of temozolomide to radiotherapy for newly diagnosed glioblastoma results in significant survival benefit with minimal additional toxicity to the patient.

 Prayson RA, Goldblum JR. Neuropathology, 1st ed. Philadelphia, PA: Elsevier; 2005.

 Rowland LP, Pedley TA. Merritt’s Neurology, 12th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2010.

 Stupp R, Mason WP, Van Den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005; 352:987–996.

12. b

Histologic type and grade are very important prognostic factors in patients with astrocytomas. The histologic type influences prognosis, and mixed variants, such as oligoastrocytomas, have a better prognosis than pure astrocytomas but worse than oligodendrogliomas. Regarding the histologic grade, a patient with a grade II astrocytoma has an average survival of 5 to 10 years, grade III has an average survival of 2 to 3 years, and grade IV has an average survival of 15 months or less. The presence of gadolinium enhancement on MRI represents a disruption of the blood-brain barrier and correlates with the WHO grade. Usually grade II tumors have no enhancement, grade III tumors have some degree of enhancement, and grade IV tumors characteristically demonstrate ring enhancement, therefore correlating with a poorer prognosis. However, it is important to note that lower grade tumors may ring-enhance and higher grade tumors may heterogeneously enhance and rarely minimally enhance.

The age of the patient is also very important, and elderly patients usually have a worse prognosis than younger patients with the same diagnosis. Performance status is also important in prognostication and when deciding the treatment options, because those with worse baseline pretreatment condition and neurologic impairment will do worse.

Pathologic findings with the presence of a necrotic center with pseudopalisading nuclei are characteristic of glioblastoma (astrocytoma WHO grade IV), and these tumors have the worst prognosis among the astrocytomas.

 Prayson RA, Goldblum JR. Neuropathology, 1st ed. Philadelphia, PA: Elsevier; 2005.

 Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology, 9th ed. New York: McGraw-Hill; 2009.

13. b

The predominant antibody in paraneoplastic optic neuropathy is anti-CRMP-5, which is associated with lung cancer. These patients present with vision loss.

The predominant antibody in paraneoplastic retinal degeneration is anti-recoverin or anti-CAR, and is associated with small cell lung cancer, thymoma, renal cell carcinoma, and melanoma. These patients present with scotomas, vision loss, predominantly nocturnal, and disc swelling.

Paraneoplastic subacute sensory neuropathy and neuronopathy are associated with anti-Hu (ANNA-1) antibodies and linked to small cell lung cancer.

Lambert-Eaton myasthenic syndrome is a paraneoplastic syndrome presenting in the setting of small cell lung carcinoma and associated with anti-voltage-gated calcium channels of the P/Q type (see Chapter 10).

Paraneoplastic chorea, presenting with bilateral choreoathetosis and in the setting of lung cancer, is associated with anti-Hu and anti-CRMP-5 antibodies.

 Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology, 9th ed. New York: McGraw-Hill; 2009.

14. c

The findings in Figure 8.3 are consistent with glioblastoma. The histopathologic specimen shows a glial neoplasm with hypercellularity, nuclear pleomorphism, necrosis, and pseudopalisading nuclei around the area of necrosis. Glioblastoma is a WHO grade IV astrocytoma, which is the most common primary brain tumor in adults and accounts for 50% of all gliomas. Grossly, it is a heterogeneous mass with necrosis and hemorrhage. Microscopically, it is very hypercellular, with nuclear atypia and abundant mitoses. Endothelial hyperplasia, necrosis, and pseudopalisading nuclei differentiate glioblastoma from other neoplasms, and from astrocytomas of lower grades.

Fibrillary astrocytoma is a diffuse astrocytoma, but it does not have necrosis or pseudopalisading. Oligodendrogliomas are hypercellular tumors with uniformly rounded nuclei and clear perinuclear haloes, giving it a “fried egg” appearance, which is not seen in this picture. Meningiomas are dural-based tumors originating from meningothelial or arachnoid cap cells, and are histologically composed of monomorphic cells with oval nuclei, sometimes with the presence of psammoma bodies, without pseudopalisading necrosis. Ependymomas are microscopically arranged in sheets of cells with round nuclei, with the presence of perivascular pseudorosettes and true ependymal rosettes.

 Prayson RA, Goldblum JR. Neuropathology, 1st ed. Philadelphia, PA: Elsevier; 2005.

15. d

With anaplastic astrocytomas, p53 mutations may be seen in nearly half of these tumors. Anaplastic astrocytoma is a WHO grade III tumor, characterized by the presence of nuclear atypia, significant cellular proliferation, and mitotic activity, but without necrosis, pseudopalisading nuclei, or endothelial hyperplasia. These tumors are highly infiltrating.

Genetic mutations are seen in these tumors, such as p53 mutation in almost half, and loss of p16 and other genes of the retinoblastoma regulatory pathway. 1p19q deletion is common in oligodendrogliomas and rare in anaplastic astrocytomas. Patients with astrocytomas WHO grade III have an average survival of 2 to 3 years.

 Prayson RA, Goldblum JR. Neuropathology, 1st ed. Philadelphia, PA: Elsevier; 2005.

16. d

This patient has a pilocytic astrocytoma, which is a WHO grade I astrocytoma and the most common glioma in children, occurring usually in the first or second decade of life. These tumors are well circumscribed, frequently located in the cerebellum, but can also be seen in the hypothalamus, third ventricle, optic nerve, spinal cord, and dorsal brain stem. In the cerebellum, they are characteristically cystic with a gadolinium-enhancing mural nodule, as depicted in Figure 8.4. In the hypothalamus and optic nerves these tumors are solid.

Most pilocytic astrocytomas are sporadic; however, neurofibromatosis type 1 is associated with these tumors, especially in the optic nerve.

Given the well-demarcated lesion, these tumors tend to be surgically curable with a good prognosis. If the tumor cannot be completely resected, radiation therapy or chemotherapy may be required.

This MRI showing a cyst with an enhancing nodule localized in the cerebellum in the age group of this patient is characteristic of pilocytic astrocytoma. The other gliomas are more common in older patients and in the supratentorial region. Acoustic schwannoma typically occurs in the cerebellopontine angle.

 Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008.

 Prayson RA, Goldblum JR. Neuropathology, 1st ed. Philadelphia, PA: Elsevier; 2005.

17. c

Pleomorphic xanthoastrocytoma (PXA) is a well-demarcated tumor, typically superficial and affecting the cortex, and most commonly encountered in the temporal lobes. It is more common in children and young adults, and manifests clinically as focal epilepsy.

On MRI, it is seen as a cyst with an enhancing mural nodule. Macroscopically, it is cystic, sometimes with calcifications. Microscopically, it is composed of pleomorphic astrocytes arranged in fascicles, with intercellular reticulin deposition. There are lipidized astrocytes in about 25% of the cases. Eosinophilic granular bodies are typically seen, and Rosenthal fibers may be seen in the periphery of the lesion.

These tumors are often surgically resectable, and the prognosis is favorable. In about 15% to 20% of the cases, PXA undergoes malignant transformation. PXA is classified as WHO grade II, unless there are foci of anaplasia, in which case it is considered grade III.

 Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008.

 Prayson RA, Goldblum JR. Neuropathology, 1st ed. Philadelphia, PA: Elsevier; 2005.

18. d

Subependymal giant cell astrocytoma (SEGA) is a benign hamartomatous tumor, WHO grade I, located in the intraventricular region, commonly in the third or lateral ventricles. It is seen in tuberous sclerosis almost exclusively, and it occurs in children and young adults, but not in elderly patients. Macroscopically, it is solid, well demarcated, noninfiltrative, and sometimes has calcifications. SEGA is surgically resectable. Microscopically, there is a glioneuronal appearance, and the cells are packed in fascicles and around blood vessels, giving the appearance of perivascular pseudorosettes. “Candle gutterings” are masses along the ventricular surface, similar histologically to SEGA, and seen in this condition.

 Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008.

 Prayson RA, Goldblum JR. Neuropathology. Philadelphia, PA: Elsevier; 2005.

19. e

Oligodendroglioma of the classic type is usually negative for glial fibrillary acidic protein (GFAP).

Oligodendrogliomas are diffuse gliomas that are infiltrating with ill-defined borders. They occur at any age, but more commonly occur in middle-aged adults (40 to 50 years of age), and are slightly more common in males (3:2). These tumors arise superficially and involve the cortex, with the most frequent location being in the frontal lobes. Given their cortical location, a common initial presenting manifestation is seizures.

WHO grade II oligodendrogliomas typically grow slowly, are seen as T2-hyperintense lesions on MRI, and are typically nonenhancing, whereas WHO grade III or anaplastic oligodendrogliomas progress more rapidly and are enhancing. Anaplastic oligodendrogliomas are hypercellular, with numerous mitoses and microvascular proliferation.

These tumors are usually negative for GFAP, except when minigemistocytic or gliofibrillary oligodendrocytes are present.

 Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008.

 Prayson RA, Goldblum JR. Neuropathology, 1st ed. Philadelphia, PA: Elsevier; 2005.

20. b

Given the age of the patient, tumor location, and pathologic features, this patient’s diagnosis is pilocytic astrocytoma.

The histopathologic specimen shown in Figure 8.5 is consistent with pilocytic astrocytoma, showing a glial neoplasm that demonstrates a biphasic pattern of compact regions along with microcystic components. There are piloid or hair-like astrocytic processes, which give the name to this tumor. In addition, Rosenthal fibers and a few eosinophilic granular bodies are seen, both of which are not pathognomonic, but are typically seen in these tumors. Eosinophilic granular bodies are also seen in pleomorphic xanthoastrocytomas and gangliogliomas. Rosenthal fibers are also seen in gliosis and in Alexander’s disease.

The clinical and histopathologic features are not consistent with the other options provided. Cerebellar hemangioblastoma are prominently vascular tumors with abundant capillaries and stromal vacuolated cells. Histopathologic features of glioblastoma multiforme include necrosis, pseudopalisading, and endothelial hyperplasia. Oligodendrogliomas are hypercellular tumors with uniformly rounded nuclei and clear perinuclear haloes, giving it a “fried egg” appearance. Meningiomas are dural-based tumors originating from meningothelial or arachnoid cap cells, and are histologically composed of monomorphic cells with oval nuclei, sometimes with the presence of psammoma bodies.

 Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008.

 Prayson RA, Goldblum JR. Neuropathology, 1st ed. Philadelphia, PA: Elsevier; 2005.

21. c

The histopathologic specimen in Figure 8.6 shows a hypercellular tumor with uniformly rounded nuclei and clear perinuclear haloes, giving it a “fried egg” appearance. There are also capillaries with a “chicken wire” appearance. These features are characteristic of oligodendrogliomas. The clear haloes are helpful in making the diagnosis; however, this appearance is caused by a delayed fixation artifact, is not pathognomonic, and may not be present in rapidly fixed specimens and frozen sections.

The histopathologic features are not consistent with the other options provided. Pilocytic astrocytoma is a glial neoplasm with piloid or hair-like astrocytic processes, which demonstrates a biphasic pattern of compact regions along with microcystic components. Histopathologic features of glioblastoma multiforme include necrosis, pseudopalisading, and endothelial hyperplasia. Ependymomas are microscopically arranged in sheets of cells with round nuclei, with the presence of perivascular pseudorosettes and true ependymal rosettes. Cerebellar hemangioblastomas are prominently vascular tumors with abundant capillaries and stromal vacuolated cells.

 Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008.

 Prayson RA, Goldblum JR. Neuropathology, 1st ed. Philadelphia, PA: Elsevier; 2005.

22. e, 23. e

This patient has an ependymoma. These types of tumors are associated with neurofibromatosis type 2 (NF2) (not NF1; see Chapter 14).

As seen in Figure 8.7, there are sheets of cells with the presence of perivascular pseudorosettes, which is characteristic of this type of tumor. Ependymomas are the third most common CNS tumor in children, more common intracranially and especially in the infratentorial region. When supratentorial, these tumors tend to occur in the periventricular region; however, they can also be present more superficially. About 10% of these tumors occur in the spinal cord, more frequently in adults.

Macroscopically, these tumors are well demarcated with a tendency to compress rather than infiltrate the parenchyma. Some cases are cystic, especially the supratentorial ones. Microscopically, they are arranged in sheets of spindled cells with round nuclei and small nucleoli. There are perivascular pseudorosettes, in which the cells surround blood vessels (as in Figure 8.7). There are also true ependymal rosettes, in which the cells are arranged around a clear space. Homer-Wright rosettes are not seen in these types of tumors (but rather in medulloblastoma).

Most ependymomas are WHO grade II. Anaplastic ependymomas are graded as WHO III, and are characterized by the presence of increased mitotic activity, hypercellularity, and microvascular proliferation. WHO grade II ependymomas may be surgically curable with a good prognosis, being the extent of resection an important prognostic factor. Radiation therapy may be used for residual disease. Prognosis is worse in patients younger than 3 years of age at presentation. Ependymomas in contact with the CSF may produce drop metastases conferring a worse prognosis.

Myxopapillary ependymoma is a WHO grade I variant that occurs almost exclusively in the filum terminale. It is more common in adults, has a red appearance grossly, and a thin collagenous capsule. These tumors have a better prognosis.

Genetically, ependymomas may be associated with chromosome 22q deletions, and spinal ependymomas may be related to NF2 mutations.

 Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008.

 Prayson RA, Goldblum JR. Neuropathology, 1st ed. Philadelphia, PA: Elsevier; 2005.

24. c

Ganglioglioma is a CNS tumor with glial and neuronal components. These tumors occur most commonly in children and young adults, arising from the temporal lobe, extending superficially, and presenting with seizures. Radiologically, the MRI may show a cyst with an enhancing mural nodule. Macroscopically, gangliogliomas are partially cystic, with solid components that may be calcified. Microscopically, there is a fibrillary background with dysmorphic ganglion cells showing nuclear pleomorphism, multinucleation, or cytoplasmic vacuolation. Other features include the presence of eosinophilic granular bodies, perivascular lymphocytic cuffing, microcystic spaces, and collagen deposition. The glial component shows glial fibrillary acidic protein positivity, whereas the neuronal component reacts with synaptophysin, chromogranin, and neurofilament.

Gangliogliomas are WHO grade I, they have a good prognosis, and the treatment is surgical resection.

 Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008.

 Prayson RA, Goldblum JR. Neuropathology, 1st ed. Philadelphia, PA: Elsevier; 2005.

25. a

Neurocytoma is a tumor that is reactive with synaptophysin, a marker of neuronal differentiation and which detects neuronal vesicle proteins.

Neurocytomas are encountered more frequently between the third and fifth decades of life. The location is intraventricular, more commonly in the lateral ventricles and in the third ventricle near the foramen of Monro. Macroscopically, they are well demarcated, gray, and friable. Microscopically, this neoplasm has round cells in a fibrillary background with prominent capillary vasculature. This tumor resembles oligodendroglioma; however, neurocytomas are immunoreactive for neuronal differentiation, but not for glial markers, being positive for synaptophysin but negative for glial fibrillary acidic protein. Ultrastructurally (on electron microscopy), neurocytoma shows neurotubules, neurofilaments, and neurosecretory granules.

These tumors are WHO grade II, with good prognosis. The treatment is surgical resection.

 Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008.

 Prayson RA, Goldblum JR. Neuropathology, 1st ed. Philadelphia, PA: Elsevier; 2005.

26. c, 27. b

The imaging findings in Figure 8.8 are consistent with a meningioma, which originates from meningothelial or arachnoid cap cells. These tumors account for 13% to 26% of primary intracranial tumors, and are more common in women, with a peak in the sixth or seventh decades of life. The most common sites include the cerebral convexities, parasagittal region, sphenoid wing, parasellar region, and spinal canal. Clinically, patients may be asymptomatic and the tumor may be found incidentally; however, depending on their location and size, meningiomas may produce focal neurologic manifestations, seizures, or headaches.

Meningiomas are dural-based tumors, often with a dural tail seen on imaging and sometimes with mass effect on the adjacent parenchyma. Calcifications may occur. These tumors are generally benign, slow growing, firm, rubbery, and well demarcated, compressing brain tissue rather than infiltrating it. However, in malignant meningiomas, there may be tissue infiltration.

Microscopically, these tumors are composed of monomorphic cells with oval nuclei, and the presence of psammoma bodies is common. However, meningiomas are very heterogeneous, with multiple histologic variants ranging in the spectrum of histologic WHO grade I, II, and III. The majority of meningiomas are syncytial, fibrous, or transitional types, which are benign variants.

Radiologically, on MRI meningiomas are isointense to gray matter on T1 and T2, with homogeneous enhancement. A dural tail may be appreciated as mentioned.

In general, most meningiomas are benign and surgically resectable, with the extent of the resection being the major predictor of recurrence. WHO grade III tumors and a high proliferative index predict a higher recurrence rate. Radiotherapy may be used for aggressive tumors.

More than half of meningiomas are associated with loss of chromosome 22, and there are associations of meningiomas with neurofibromatosis type 2, previous radiation, and breast carcinoma.

 Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008.

 Prayson RA, Goldblum JR. Neuropathology, 1st ed. Philadelphia, PA: Elsevier; 2005.

28. a

Figure 8.9 shows a tumor characterized by prominent capillary vasculature and stromal cells showing a vacuolated cytoplasm. This is consistent with hemangioblastoma.

Hemangioblastomas are benign, vascular tumors, and the most common primary cerebellar neoplasm in adults. They can occur at any age, with a peak incidence between 25 and 40 years, being slightly more common in males. Macroscopically, they are well demarcated and cystic. Histopathologically, there are abundant capillaries and stromal vacuolated cells. They may present with mass effect and CSF obstruction, leading to increased intracranial pressure. About 10% of these tumors secrete an erythropoietin-like substance leading to secondary polycythemia. MRI demonstrates a cyst with an enhancing mural nodule.

This tumor is WHO grade I, and can be resected surgically. Hemangioblastomas are associated with von Hippel-Lindau (VHL) in about 25% of the cases, related to mutations in the VHL gene on chromosome 3p25–26.

 Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008.

 Prayson RA, Goldblum JR. Neuropathology, 1st ed. Philadelphia, PA: Elsevier; 2005.

29. a

Figure 8.10 shows a hypercellular neoplasm, with a sheet-like proliferation of small blue cells and a high nuclear-to-cytoplasm ratio, characteristic of medulloblastoma. Homer-Wright pseudorosettes, even though not appreciated in this picture, are seen in about a third of cases. Macroscopically, medulloblastomas are soft tumors, with necrosis and hemorrhage.

Medulloblastoma is a rapidly growing and invasive tumor, which arises from the cerebellum. It is seen in children, and accounts for 20% of childhood brain tumors.

The histopathologic features are not consistent with the other options provided. Oligodendrogliomas are hypercellular tumors with uniformly rounded nuclei and clear perinuclear haloes, giving it a “fried egg” appearance. Pilocytic astrocytoma is a glial neoplasm with piloid or hair-like astrocytic processes, and demonstrates a biphasic pattern of compact regions along with microcystic components. Meningiomas are dural-based tumors originating from meningothelial or arachnoid cap cells, histologically composed of monomorphic cells with oval nuclei, sometimes with the presence of psammoma bodies. Histopathologic features of glioblastoma multiforme include necrosis, pseudopalisading nuclei, and endothelial hyperplasia.

 Prayson RA, Goldblum JR. Neuropathology, 1st ed. Philadelphia, PA: Elsevier; 2005.

 Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology, 9th ed. New York: McGraw-Hill; 2009.

30. c

Pineocytomas and pineoblastomas are tumors arising from the pineal gland parenchyma, presenting with various manifestations, including ophthalmologic findings such as Parinaud syndrome, brain stem and cerebellar manifestations, features of increased intracranial pressure, and hypothalamic dysfunction.

Pineocytomas are more frequent in young adults. These tumors are well demarcated and homogeneous. Histopathologically, this tumor is composed of small uniform cells that resemble pineocytes, with low mitotic activity. There may be rosette formations.

Pineoblastomas are more frequent in children and macroscopically are soft and poorly demarcated, with areas of necrosis and hemorrhage. The cells may resemble those of other embryonal tumors, such as medulloblastomas, and there is significant proliferation of small round cells with high nuclear-to-cytoplasmic ratio, and prominent mitotic activity. These cells lack differentiation and resemble primitive neuroectodermal tumors, and not mature pineocytes. Pineoblastomas are associated with a deletion on chromosome 11q, and may spread via the craniospinal axis or may metastasize. The prognosis of pineocytomas is better than that of pineoblastomas.

 Prayson RA, Goldblum JR. Neuropathology, 1st ed. Philadelphia, PA: Elsevier; 2005.

 Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology, 9th ed. New York: McGraw-Hill; 2009.

31. d

Several types of benign cysts arise in the neuroaxis. These cysts can be resected if symptomatic, and do not undergo malignant degeneration.

Colloid cysts arise near the foramen of Monro, and may produce several manifestations including headache and mental status changes, and if there is obstruction of the foramen of Monro, patients may present with drop attacks, acute hydrocephalus, and even sudden death. Symptoms may be intermittent, and syncope and other symptoms may be positional, occurring when the patient bends forward or with Valsalva. Radiologically, these cysts have increased signal on T1, with no enhancement. Colloid cysts have a thin-walled lining and contain thick and cloudy gelatinous fluid. Microscopically, there is a single layer of columnar ciliated or goblet cells. The treatment is surgical resection, and sometimes shunt placement is required for management of hydrocephalus.

Epidermoid and dermoid cysts arise from ectopic ectodermal tissue. Epidermoid cysts occur in young adults and arise from the cerebellopontine angle. On MRI, epidermoid cysts have CSF intensity on T2, being slightly hyperintense to CSF fluid on FLAIR. They have a characteristic restricted diffusion appearance on DWI, which helps to distinguish these cyst from arachnoid cysts. Epidermoid cysts are microscopically lined by squamous-type epithelium filled with keratinaceous material.

Dermoid cysts arise in children, and tend to occur in the cerebellar vermis, parasellar, or parapontine region and in the lumbosacral region in the spinal canal. They are a “pearly” white structure, with a content similar to epidermoid cysts, and lined by squamous epithelium; however, dermoid cysts also contain hair follicles, sebaceous glands, and sweat glands. Dermoid cysts can rupture, and the content can incite a chemical meningitis characterized by a granulomatous inflammation.

Arachnoid cysts are basically a cystic space bound by arachnoid membranes, with a location associated with the meninges, predominantly in the temporal lobe region. They are lined by arachnoid cap cells.

Rathke’s cleft cysts occur in between the anterior and posterior hypophysis. They have a thin-walled lining containing a cloudy fluid, and are lined by columnar epithelium with ciliated and goblet cells.

 Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008.

 Prayson RA, Goldblum JR. Neuropathology, 1st ed. Philadelphia, PA: Elsevier; 2005.

32. d

In medulloblastomas, a diagnosis at a younger age (usually younger than 3 years of age) confers a poorer prognosis.

Medulloblastomas are embryonal tumors that arise from pluripotential cells and are encountered in children, more commonly in males, and located in the posterior fossa, more specifically in the cerebellum. The clinical presentation includes manifestations of increased intracranial pressure, hydrocephalus, and cerebellar findings. The most common genetic defect is on chromosome 17. This tumor can metastasize or spread via CSF, and therefore, MRI of the entire neuroaxis should be obtained.

Treatment involves maximal surgical resection, in addition to chemotherapy and radiation therapy, with survival rates up to 80% at 5 years.

A desmoplastic variant confers a better prognosis. Features of poor prognosis include early age at the onset (younger than 3 years of age), incomplete resection, presence of brain stem invasion, metastasis, large cell variants, glial differentiation, and N-myc transcription factor amplification.

 Prayson RA, Goldblum JR. Neuropathology, 1st ed. Philadelphia, PA: Elsevier; 2005.

 Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology, 9th ed. New York: McGraw-Hill; 2009.

33. e

The pathologic features in Figure 8.11 are typical of a dysembryoplastic neuroepithelial tumor (DNET), demonstrating prominent clear spaces that seem to contain ganglion cells. In between these clear spaces, there are multiple cells and a glial component that resembles an oligodendroglioma.

DNET is a benign superficial tumor that is an important cause of refractory seizures in children. These tumors are located in the cortical or juxtacortical region, most commonly in the temporal lobe. The MRI shows a nodular or cystic lesion that is hyperintense on T2-weighted images and does not enhance with contrast. It grows very slowly, and macroscopically, it has a multinodular architecture, with mucinous cysts. Histologically, it is seen as multiple areas in which ganglion cells appear to float within mucin-filled spaces (“floating neurons”). In between these nodules, there is a component with more glial characteristics, sometimes resembling an oligodendroglioma. At the edges of these lesions, there may be cortical dysplasia.

DNET is a WHO grade I tumor, and surgical resection is helpful for the cure or control of the seizures.

 Prayson RA, Goldblum JR. Neuropathology, 1st ed. Philadelphia, PA: Elsevier; 2005.

 Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology. 9th ed. New York: McGraw-Hill; 2009.

34. b, 35. e

This patient has a lymphoma, likely primary CNS lymphoma (PCNSL) given the parenchymal invasion of lymphocytes with an angiocentric pattern. Surgical resection does not play a role in the treatment of lymphomas.

PCNSL occur predominantly in immunocompromised patients, such as patients with AIDS and posttransplant patients. In these cases they are frequently associated with Epstein-Barr virus (EBV). PCNSL can also occur in immunocompetent hosts; however, this is rare, and there is a lower association with EBV.

PCNSL is usually a diffuse, large B-cell lymphoma, and rarely caused by T-cell proliferation. In contrast to secondary invasion by lymphomas from other primary sites, PCNSL invades the parenchyma more than the leptomeninges, and histologically, it is characterized by proliferation and diffuse infiltration of atypical lymphocytes with an angiocentric pattern as seen in Figure 8.12. These neoplasms can be single or multicentric, and can involve the corpus callosum. PCNSL can also involve the eye, and therefore, an ophthalmology evaluation is warranted to examine the vitreous for lymphoma cells.

Clinically, the presentation is variable, manifesting with headaches, signs of increased intracranial pressure, seizures, focal neurologic deficits, or alteration in the mental status. MRI shows a lesion with T2 hyperintensity, edema, and contrast enhancement.

The prognosis is poor, with 5-year survival rates of 25% to 45%, being much worse in immunocompromised patients.

This neoplasm is steroid responsive, and steroids should be avoided before biopsy because they may reduce the yield of this diagnostic test. However in cases of emergency, especially in the presence of significant mass effect and herniation, steroid use may be required.

Surgery is not indicated because this neoplasm is often deep and multicentric. The treatment includes radiation therapy and chemotherapy, with agents such as cytosine arabinoside and intrathecal methotrexate. This combination prolongs survival; however, it is associated with leukoencephalopathy and systemic side effects. In patients with HIV-related PCNSL, highly active antiretroviral therapy is the treatment of choice.

Given the clinical and histopathologic features shown, this is not a glioblastoma, oligodendroglioma, meningioma, or ependymoma.

 Prayson RA, Goldblum JR. Neuropathology, 1st ed. Philadelphia, PA: Elsevier; 2005.

 Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology, 9th ed. New York: McGraw-Hill; 2009.

36. b

This is a craniopharyngioma, which is most common in children, but has a bimodal age distribution and is also seen in adults.

Figure 8.13 shows a tumor with multicystic components, characterized by proliferation of cords of epithelial-appearing cells, with a palisade of basaloid cells toward the lumen of the cysts. This is consistent with a craniopharyngioma. Craniopharyngiomas are benign epithelioid tumors that originate from remnants of the Rathke’s pouch and arise in the sellar region, where they grow to produce manifestations from mass effect on adjacent structures, such as the optic chiasm, pituitary, hypothalamus, bony structures, and ventricular system, even to the point of being able to obstruct CSF flow. Common manifestations are therefore visual disturbances, endocrine deficiencies, diabetes insipidus, and findings of increased intracranial pressure. Craniopharyngiomas occur in a bimodal distribution, seen with a peak incidence in childhood and middle-aged adults. Macroscopically, these tumors are partially solid with a cystic component, frequently filled with lipid- and cholesterol-rich brown fluid, also called “machine-oil–like fluid,” which if spilled, may cause a xanthogranulomatous inflammation. Microscopic calcifications, keratin, and xanthogranulomatous inflammation are seen more commonly in the adamantinomatous variant. In the papillary variant, the sheets of cells form pseudopapillae.

These tumors are in general surgically resectable. They have a benign behavior, but may recur if there is incomplete resection.

 Prayson RA, Goldblum JR. Neuropathology, 1st ed. Philadelphia, PA: Elsevier; 2005.

 Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology, 9th ed. New York: McGraw-Hill; 2009.

37. d

Figure 8.14 shows a proliferation of epithelial cells in a papillary pattern lining fibrovascular cores, consistent with choroid plexus papilloma, which is a WHO grade I tumor.

Choroid plexus papillomas are tumors of childhood, and most commonly arise from the lateral ventricles, followed by the fourth ventricle and then the third ventricle. Clinically, they may be asymptomatic, or present with hydrocephalus and manifestations of increased intracranial pressure, sometimes due to a combination of obstructed flow and increased CSF production.

Choroid plexus papillomas are circumscribed masses composed of epithelium lining fibrovascular cores, resembling normal choroid plexus. In contrast to papillomas, choroid plexus carcinomas are invasive, with nuclear pleomorphism, demonstrating atypia, mitosis, and necrosis.

Choroid plexus papillomas are surgically resectable and considered low grade or WHO grade I. Choroid plexus carcinomas are higher grade (WHO grade III), and after surgical resection, radiotherapy and chemotherapy may be needed.

 Prayson RA, Goldblum JR. Neuropathology, 1st ed. Philadelphia, PA: Elsevier; 2005.

 Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology, 9th ed. New York: McGraw-Hill; 2009.

38. e

Chordomas are invasive osseo-destructive tumors encountered in adults, more commonly in males, and arise from remnants of the primitive notochord. They are located most commonly in the clivus and sacrococcygeal region. If in the clivus, they may present clinically with headaches, neck pain, and multiple cranial neuropathies due to brain stem compression. If in the sacrococcygeal region, they may present with sphincter dysfunction and pain.

These tumors are locally invasive and tend to destroy the bone, which is appreciated on radiologic studies such as CT and MRI. Grossly, this tumor is infiltrative and lobulated. Microscopically, there is a lobulated pattern with fibrovascular septa and cords of epithelioid cells. Vacuolated cells are present and are called physaliphorous cells.

The treatment is surgical excision and sometimes radiotherapy for residual disease. There may be recurrences from residual tumor.

 Prayson RA, Goldblum JR. Neuropathology, 1st ed. Philadelphia, PA: Elsevier; 2005.

 Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology, 9th ed. New York: McGraw-Hill; 2009.

39. a

This patient has a vestibular schwannoma. These are tumors that occur more commonly in the fourth and fifth decades, and most commonly arise from the vestibular portion of cranial nerve VIII. They grow in the cerebellopontine angle, and may compress the brain stem and erode into the internal auditory meatus. Clinically, they grow slowly and may be asymptomatic, or present with hearing loss, tinnitus, and in some cases cerebellar findings given that the cerebellar peduncles are compressed. Radiologically, they are seen as circumscribed isointense tumors with contrast enhancement as seen in Figure 8.15. The location and radiologic appearance of the tumor as shown in Figure 8.15 distinguish it from the other choices. It is extra-axial (not within the brain parenchyma) and is not within the ventricular system. This is not a location typical for metastatic lesions. Given the clinical and radiologic findings, this patient does not have an oligodendroglioma, cerebellar hemangioblastoma, ependymoma, or metastatic tumor.

 Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008.

 Prayson RA, Goldblum JR. Neuropathology, 1st ed. Philadelphia, PA: Elsevier; 2005.

40. b, 41. c

Metastatic lesions are more common than primary brain tumors. Eighty percent of brain metastases are supratentorial and 20% intratentorial. Intracranial metastatic lesion can affect the skull and dura and brain parenchyma or produce a meningeal carcinomatosis.

The most common source of metastasis to the brain is the lung, followed by breast and then melanoma. Other tumors that may produce brain metastasis include gastrointestinal tumors especially from the colon and rectum—also, kidney cancer and tumors originating from the gallbladder, liver, thyroid, testicle, uterus, ovary, and pancreas. It is very rare to have parenchymal brain metastases originating from the prostate, esophagus, oropharynx, and skin (other than melanoma). Colon and pelvic cancers have a tendency to spread to the posterior fossa.

Metastatic lesions can be multiple or single. Multiple metastases are seen with small cell carcinomas and melanomas. Those that are frequently found as single metastasis originate from the kidney, breast, thyroid, or adenocarcinoma of the lung. Hemorrhagic metastases are seen with melanoma, choriocarcinomas, non–small cell carcinomas, thyroid carcinomas, and renal cell carcinomas.

Patients harboring metastasis typically present with a seizure, focal neurologic findings, headaches, and sometimes with increased intracranial pressure. Symptom onset is typically relatively rapid and abrupt rather than gradual.

The treatment of brain metastasis includes brain irradiation, surgical intervention for solitary metastasis in some cases, and chemotherapy. Steroids play a significant role in the treatment of surrounding edema.

 Prayson RA, Goldblum JR. Neuropathology, 1st ed. Philadelphia, PA: Elsevier; 2005.

 Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology, 9th ed. New York: McGraw-Hill; 2009.

42. c

The histopathologic findings in Figure 8.16 are consistent with a vestibular schwannoma.

Schwannomas most commonly arise from the vestibular portion of CN VIII and grow in the cerebellopontine angle. Grossly, they have a yellowish color and are well demarcated. Histologically, there is a biphasic pattern with a more compact phase (or Antoni A area) and a looser pattern (or Antoni B area). The cells and nuclei tend to be elongated, sometimes with an arrangement in a palisade configuration, which is called Verocay body, as seen in Figure 8.16. This figure shows an Antoni A pattern. Immunohistochemically, these tumors are S-100 positive.

Vestibular schwannomas are associated with neurofibromatosis type 2, and the presence of bilateral tumors is diagnostic for this latter condition.

These tumors are benign, categorized as WHO grade I, and surgically resectable. Gamma knife may also be a therapeutic option.

 Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008.

 Prayson RA, Goldblum JR. Neuropathology, 1st ed. Philadelphia, PA: Elsevier; 2005.

43. c

The imaging findings in Figure 8.17 and appearance of the lesion in Figure 8.18 are consistent with a pituitary adenoma. Pituitary adenomas greater than 1 cm in size are classified as macroadenomas, whereas those less than 1 cm in size are classified as microadenomas. Most pituitary adenomas are nonsecretory; of the secretory ones, prolactin-secreting adenomas, so-called prolactinomas, are most common, though those secreting growth hormone, ACTH, and thyroid-stimulating hormone also occur. Follicle-stimulating hormone–secreting adenomas may occur; luteinizing hormone–secreting adenomas are rare. Patients may be asymptomatic, as in this patient’s case in which the visual field deficit was detected incidentally. In women, symptoms including galactorrhea and amenorrhea lead to earlier diagnosis, particularly in the case of prolactinomas. In men, prolactinomas may present with impotence. Endocrine disturbances may occur with nonsecretory adenomas when the lesion is large enough to compromise normal pituitary tissue function. Other symptoms include headache, ophthalmoparesis, and vision loss. Pressure on or invasion into the cavernous sinus may lead to cranial neuropathies.

Pituitary adenomas are the most common masses in the sellar region. The lesion is isointense on T1, and enhances almost homogeneously with contrast, as seen in Figure 8.17Figure 8.18 shows evidence of monomorphic eosinophilic cells. Besides tumors of pituitary origin, other tumors that may occur in the sellar region include gliomas, meningiomas, chordomas, metastases, and others. Pituitary apoplexy, or hemorrhage into, most commonly, a pituitary macroadenoma, presents with sudden severe headache, ophthalmoparesis, and in some cases evidence of increased intracranial pressure.

The histopathologic findings are not consistent with a craniopharyngioma or Rathke’s cleft cyst. Craniopharyngiomas are benign epithelioid tumors that originate from remnants of the Rathke’s pouch and arise in the sellar region, where they grow to produce manifestations from mass effect on adjacent structures. Craniopharyngiomas are multicystic, with squamous epithelial cells and sometimes calcifications.

Rathke’s cleft cysts occur in between the anterior and posterior hypophysis. They have a thin-walled lining containing a cloudy fluid, and they are lined by columnar epithelium with ciliated and goblet cells.

 Aminoff MJ. Neurology and General Medicine, 4th ed. Philadelphia, PA: Elsevier; 2008.

 Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008.

44. a

Figure 8.19 shows a lesion with typical characteristics of metastasis. Metastases are round and demarcated, located in the gray-white junction, and hyperintense on T2-weighted images, with significant enhancement with gadolinium, and prominent surrounding vasogenic edema, which is appreciated on the FLAIR image in Figure 8.19 as hyperintensity around the main lesion.

Meningiomas are dural-based tumors, which is not the case in Figure 8.19. Low-grade diffuse fibrillary astrocytomas will not show this degree of edema. Glioblastoma is an aggressive lesion that demonstrates surrounding edema; however, it usually will have a more heterogeneous enhancement pattern with areas of necrosis. This is not a location for an ependymoma, which will have a closer relationship with the ventricular surface.

 Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008.

45. a

Various immunohistochemical markers are utilized to help in the diagnosis and typification of certain neoplasms. Glial fibrillary acidic protein (GFAP) is positive with glial intermediate filaments, cytokeratin is positive with epithelial intermediate filaments, Melan-A and HMB-45 are positive with melanocytic cells, CD45 is a marker of lymphocytes, CD3 for T cells, and CD20 for B cells. Ki-67 is a marker of nuclear proliferation.

In this case, with positive GFAP and very high percentage of Ki-67, the most likely diagnosis is an astrocytoma. Given that GFAP can be positive in gliosis, Ki-67 helps distinguish between the two. A carcinoma will likely be cytokeratin positive. Melanoma will likely show Melan-A and HMB-45 positivity. Absence of positive markers for lymphocytes makes lymphoma unlikely.

 Prayson RA, Goldblum JR. Neuropathology, 1st ed. Philadelphia, PA: Elsevier; 2005.

46. b

Pilocytic astrocytoma is a WHO grade I, not grade II, tumor. Astrocytomas are neoplasms that originate from the neuroglia. These may arise from different regions of the CNS, including the brain, cerebellum, hypothalamus, optic nerve, optic chiasm, brain stem, and spinal cord. The location is influenced by age, and in adults, they are most frequently encountered in the cerebral hemispheres. The clinical presentation may be variable, with headaches, focal neurologic manifestations, and frequently seizures.

The WHO grades these tumors on the basis of the St. Anne–Mayo grading system, using extent of atypia, mitoses, endothelial hyperplasia, and necrosis as criteria. Astrocytomas are classified as at least WHO grade II in the presence of atypia. Anaplastic astrocytomas are classified as WHO grade III on the basis of the presence of atypia and mitotic activity. Glioblastoma multiforme are WHO grade IV, having endothelial hyperplasia and necrosis. Pilocytic astrocytoma is a WHO grade I well-circumscribed tumor, frequently located in the cerebellum, but can also be seen in the hypothalamus, third ventricle, optic nerve, spinal cord, and dorsal brain stem.

Astrocytomas can also be classified as diffuse astrocytomas, pilocytic astrocytomas, pleomorphic xanthoastrocytomas, and subependymal giant cell astrocytomas. Diffuse astrocytomas can be subdivided according to the predominant histologic cell type (see questions 2 and 3).

 Prayson RA, Goldblum JR. Neuropathology, 1st ed. Philadelphia, PA: Elsevier; 2005.

 Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology, 9th ed. New York: McGraw-Hill; 2009.

47. b

Figure 8.20 shows signal hyperintensity in both mesial temporal lobes, as well as a PET scan demonstrating increased fluorodeoxyglucose uptake in the mesial temporal lobes bilaterally. These findings are consistent with limbic encephalitis. In young patients with paraneoplastic limbic encephalitis, a testicular germ cell tumor may be the cause, and most often associated with anti-Ma antibodies, not anti-Hu.

Paraneoplastic encephalomyelitis may affect various parts of the CNS. Paraneoplastic limbic encephalitis is a subset of this syndrome, in which bilateral temporal lobes and other limbic structures are involved. These patients present with a neuropsychiatric syndrome characterized by personality changes, depression, agitation, hallucinations, psychosis, and a confusional state. Typically, these patients have amnesia, with prominent short-term anterograde component. Sometimes seizures occur as well. The onset is usually gradual and progressive over weeks to months, but there are cases of more rapid evolution. CSF may show mild pleocytosis and increased protein. The MRI demonstrates a characteristic hyperintensity in bilateral mesial temporal lobes, as shown in Figure 8.20. Histopathologically, there is inflammation with perivascular lymphocytes and monocytes, microglial proliferation, neuron loss, and foci of necrosis.

This syndrome presents in patients with small cell lung cancer associated with anti-Hu (ANNA-1) antibodies. In young males, it may also be seen associated with testicular germ cell tumors, in which case the most common antibody encountered is anti-Ma. An autoimmune, nonparaneoplastic limbic encephalitis associated with voltage-gated potassium channel antibodies (anti-VGKC antibodies) may lead to a similar presentation.

Treatment involves addressing the primary neoplasm. Some cases are responsive to steroids or other immunomodulatory therapies such as plasmapheresis or intravenous immunoglobulins.

A paraneoplastic encephalitis has been reported in patients with ovarian teratomas associated with antibodies to NMDA receptors. This type of encephalitis manifests with psychiatric symptoms, amnesia, seizures, dyskinesias, autonomic dysfunction, and decreased level of consciousness. In these patients, tumor resection and immunotherapy lead to improvement, and in some cases, to full recovery.

 Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008.

 Dalmau J, Tuzun E, Wu HY, et al. Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol. 2007; 61:25–36.

 Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology, 9th ed. New York: McGraw-Hill; 2009.

48. b

The prognosis in oligodendrogliomas is better than in astrocytomas. Other factors that influence prognosis include age of the patient (better survival with younger patients), presurgical performance status (worse prognosis with poorer baseline functional and neurologic status), bulk of resection (the greater the extent of resection the better), and genetic alterations. Important genetic alterations are chromosome 1p and 19q codeletions, which occur in 50% to 80% of the cases, and are associated with a better prognosis, enhanced survival, and better response to chemotherapy, radiation therapy, or both. Mutation of p53 is not typically seen in oligodendrogliomas, and its presence suggests the possibility of an astrocytic neoplasm. Deletion of the chromosomal region p16 is more commonly seen in anaplastic astrocytomas and glioblastomas, and is associated with progression.

Treatment of oligodendrogliomas involves surgical resection, chemotherapy, and radiation therapy. The chemotherapy used includes temozolomide, which has replaced PCV (procarbazine, lomustine, and vincristine).

 Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008.

 Prayson RA, Goldblum JR. Neuropathology, 1st ed. Philadelphia, PA: Elsevier; 2005.

49. c

The principle of autonomy is based on the premise that patients are their own ultimate decision makers. Autonomy contrasts with physician paternalism, which dominated the physician-patient relationship in the past, in which the physician was viewed, and viewed him- or herself, as the authoritative decision maker that would simply tell the patient what was best for him or her. The modern-day physician-patient relationship is built around patient autonomy, creating room for shared decision making, in which the physician presents treatment options to the patient and provides the education necessary for the patient to make a decision with the help and support of the physician.

In the case presented, the physician has offered all treatment options to the patient, and the patient has made an informed decision to have only symptomatic treatment. The patient clearly understands the implications of his decision, and although the physician does not agree with it, he or she will still support the patient and care for him. Assessment of the patient’s capacity to make decisions for himself is not indicated in this case as the patient clearly demonstrates understanding of the consequences of his or her decision. Denying the patient further care because of the decision the patient has made is clearly the incorrect answer. Making sure to frequently reassess the patient’s understanding and discussing treatment options at later encounters is important, but use of derogatory remarks to coerce the patient into a specific treatment option is clearly not in line with respecting patient autonomy. Option e is a demonstration of paternalism; while physicians should clearly state their medical opinion on the basis of best evidence as to what they feel the best course of action would be, shared decision making, taking into account the patient’s values and wishes, is the basis of respecting patient autonomy.

 Jonsen A, Siegler M, Winslade W. Clinical Ethics: A Practical Approach to Ethical Decisions in Clinical Medicine, 6th ed. New York: McGraw-Hill; 2006.