1. Pathology of CNS tumors (II)
Dr. Noha R. Noufal Assistant Professor of Pathology

2. Objectives of the lecture:
Upon completion of this lecture, students should be able to:
Appreciate how the anatomy of the skull and the spinal column influences the prognosis of both benign and malignant primary CNS tumors.
List the principal clinicopathological features of some of the main types of tumors that can arise within the central and the peripheral nervous systems
اسم ورقم المقرر – Course Name and No.
6/2/2019

3. Medulloblastomas (Embryonal/ Primitive neuroectoderm Neoplasm)
Occurs predominantly in children
Located in the midline of the children cerebellum, but lateral locations are more often found in adults
Rapid growth may occlude the flow of CSF, leading to hydrocephalus
The tumor disseminate through CSF fluid
The tumor is highly malignant & associated with bad prognosis

4. Medulloblastomas (Embryonal/ Primitive neuroectoderm Neoplasm)
Medulloblastoma cells have a tendency to:
Infiltrate through cerebellar cortex
Penetrate the pia
seed into the subarachnoid space
Medulloblastoma is radiosensitive
اسم ورقم المقرر – Course Name and No.
6/2/2019

5. Medulloblastomas Gross: Microscopic:
The tumor is often well circumscribed, gray, and friable
Microscopic:
Extremely cellular tumor, with sheets of anaplastic cells
Individual tumor cells are small, with scant cytoplasm and hyperchromatic nuclei
Mitoses are abundant
The tumor may express neuronal (neurosecretory granules or Homer Wright rosettes)

6. GROSS The tumor is often well circumscribed, gray, and friable.
Cerebellum and brainstem, medulloblastoma – Gross, sagittal section
The tumor in this image replaces much of the cerebellum, compresses the fourth ventricle, and distorts the brainstem
The tumor is often well circumscribed, gray, and friable.

7. Microscopic appearance of medulloblastoma
Multiple nodules of small cells in medulloblastoma
Homer Wright rosettes

8. Meningiomas
Meningiomas are non glial tumors arising from meningothelial cells of the arachnoid
It is a common benign neoplasm in adult usually attached to dura
Meningiomas may be found along the external surfaces of the brain and within the ventricular system
Slow growing ,common in females
Previous radiation therapy is a risk factor for development of this tumors

9. Meningiomas Extension into the overlying bone may be present
Most meningiomas have a relatively low risk of recurrence or aggressive growth (WHO grade I)
اسم ورقم المقرر – Course Name and No.
6/2/2019

10. Meningiomas
Gross:
Meningiomas are usually rounded encapsulated masses with well-defined dural bases
Tumor mass compress underlying brain but are easily separated from it
Dural base
Mass

11. Microscopically, Characterized by formation of whorls by spindle cells and by psammoma bodies
Menengothelial whorls

12. Grading of Meningiomas:
WHO Grade I / Meningiomas
Commonest and shows varied histological patterns
Grade II /Atypical meningioma
Characterized by mitoses and necrosis
Lesions with a higher rate of recurrence and more Aggressive local growth
Grade III /Anaplastic meningioma
Extensive mitoses and necrosis
Aggressive tumoral behavior

13. Summary Bad prognosis Densely cellular,sheets of anaplastic blue clles
Microscopic
Macroscopic
Location
Incidence
Types
Bad prognosis
Densely cellular,sheets of anaplastic blue clles
Hommer Wright rosettes
Well circumscribe, gray and friable
cerebellum
Children
Medulloblastoma
Increased grim prognosis with grade
Whorls of meningothelial cells
Psammoma bodies.
Well defined mass attached to dura
Arachnoid meningothelial cells
Attached to dura
Adults
Meningiomas
(WHO I)
Increased cellularity
Higher atypia
Frequent mitosis
Aggressive local growth and invasion
Atypical Meningiomas
(WHOII)
Anaplastic cells
Atypical mitosis
necrosis
Anaplastic Meningiomas
(WHO III)

14. Metastatic Tumors
The terms metastatic brain tumor or brain metastasis refer to cancer that begins elsewhere in the body and spreads to the brain
Brain metastasis can present as a single tumor or multiple tumors
Metastatic tumors account for approximately 25%-50%of intracranial tumors
The most common primary sites are lung, breast, skin (melanoma), kidney, and gastrointestinal tract

15. Metastatic Tumors
Dissemination occurs by the bloodstream, less often by direct invasion from neighboring malignancies
Common sites of metastases are the brain parenchyma and the meninges, less often the spinal cord and peripheral nerves
Metastases to the nervous system are serious, even fatal, complications of malignancies
اسم ورقم المقرر – Course Name and No.
6/2/2019

16. Brain, metastatic carcinoma – Gross, coronal section
This section contains at least three metastatic deposits. Carcinomas that metastasize to the brain parenchyma reach the brain via arterial channels. Similar to other embolic processes, parenchymal metastases are most commonly encountered in the territory of the middle cerebral artery, often implant at gray-white junctions, and are often multiple. They are typically well circumscribed. This patient's primary tumor was in the lung. 
اسم ورقم المقرر – Course Name and No.
6/2/2019

17. Peripheral Nerve Sheath Tumors
These tumors arise from cells of the peripheral nerve, including Schwann cells, perineural cells, and fibroblasts
In most peripheral nerve sheath tumors, the neoplastic cells show evidence of Schwann cell differentiation
Peripheral nerve sheath tumors are important features of the familial tumor syndromes NF1 and NF2
Such tumors may manifest as
Soft tissue masses
With pain or loss of function related to Compression of nerves or other surrounding structures

18. Peripheral Nerve Sheath Tumors
These tumors usually occur in adults
These tumors include:
Schwanoma
Neurofibroma
Malignant peripheral nerve sheath tumors
Schwannomas and neurofibromas are benign nerve sheath tumors
اسم ورقم المقرر – Course Name and No.
6/2/2019

19. Schwannoma Benign tumor composed of Schwann cells
Found in all ages, most commonly in the fourth through sixth decades
Most commonly involves peripheral nerves in skin and subcutaneous tissues of the head and neck region and flexor surfaces of extremities
Accounts for about 10% of intracranial tumors (usually arises from sensory cranial nerves, most often eighth cranial nerve) and about 30% of spinal tumors

20. Schwannoma
Associated with neurofibromatosis type 2 (NF2) (bilateral vestibular schwannomas)
Peripheral tumors typically present as asymptomatic masses
Spinal tumors often present with radicular pain or signs of spinal cord compression
tumors of cranial nerve VIII cause hearing difficulties or tinnitus.
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6/2/2019

21. Schwannoma Gross: Encapsulated, tumors that abut the nerve of origin
Microscopic:
Mixture of Hypercellular (Antoni A) and hypocellular areas (Antoni B) in schwannoma
Antoni (A): spindle cells with nuclear palisading
Antoni (B): the spindled cells spared by mucoid extracellular matrix
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6/2/2019

22. Antoni A area with the nuclei of tumor cells aligned in palisading rows
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6/2/2019

23. Neurofibroma
Common benign tumor composed of Schwann cells, fibroblasts, and perineural cells
Occur sporadically most frequently but also associated with NF1
Neurofibromas may manifest as
a sporadic subcutaneous nodule
as a large, poorly defined soft tissue lesion
a growth within a nerve

24. Neurofibroma
Neurofibromas are not encapsulated The cells have wavy and pointed ends nuclei The background stroma often contains loose wavy collagen bundles but also can be myxoid or contain dense collagen Residual axons are found embedded within the diffuse neoplastic Schwann cell proliferation
اسم ورقم المقرر – Course Name and No.
6/2/2019

25. No capsule Wavy nuclei with fibrous tissue No pleomorphism
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26. Neurofibromatosis Type 1 (NF1)
This is an autosomal-dominant disorder caused by mutations in the tumor suppressor neurofibromin
The tumors arising in the setting of NF1 include:
Neurofibromas
Malignant peripheral nerve sheath tumors
Optic gliomas, and other glial tumors
Patients with NF1 exhibit:
learning disabilities
seizures
skeletal abnormalities
vascular abnormalities
pigmented nodules of the iris & pigmented skin lesions

27. Neurofibromatosis Type 2 (NF2)
This is an autosomal-dominant disorder caused by loss of function mutation of the merlin gene
NF2 patients are at risk of developing:
multiple schwannomas
meningiomas
ependymomas
Neurofibromas are NOT a feature of NF2

28. Summary of peripheral Nerve Sheath Tumors
Prognosis
Microscopic
Macroscopic
origin
Incidence
Types
Benign
Good prognosis
Mixture of Antoni (A) and Antoni (B)
Encapsulated, circumscribed mass
Schwann cells of peripheral nerves
May be sporadic in adult & NF2 in young
Shwannoma
May develop MPNST
wavy nerve fibers
Non capsulated mass
peripheral nerve fiber elements
Occurs with NF1
Neurofibroma

29. Take Home Message
Histological distinction between benign and malignant lesions may be more subtle in comparison to other body system.
Even low grade tumors or benign tumors can have a poor clinical outcome depending on their location.
Glioblastoma is the most aggressive and poorly differentiated glial tumor.
Metastatic spread of brain tumors to other regions is rare, but brain is not comparable protected against spread of tumors elsewhere.