1. Pathology of CNS tumors(I)
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

3. Overview Low incidence.
About 50% to 75% are primary tumors, and the rest are metastatic.
Occurs at all ages.
Account second most common tumors in children,
Most of the CNS tumors in children arise in the posterior fossa.
Common types occur in children are (pilocytic astrocytoma (Benign), medulloblastoma (Malignant).
While most of the CNS tumors in adults arises in the cerebral cortex. The most common primary malignant tumor in adult is Glioblastoma.

4. Etiology
Both genetic predisposition and environmental agents are factors in the etiology of nervous system tumors
Some brain tumors develop in patients afflicted with certain hereditary syndromes for example:
Neurofibromatosis type 1: gliomas
Neurofibromatosis type 2: Schwannomas, Ependymomas, meningiomas

5. Classification of Brain Tumors
Primary brain tumors.
Gliomas (80% of tumors in adult):
(Astrocytoma, Oligodendrogliomas, Ependymomas).
Meningiomas (15% of tumors in adults).
Undifferentiated composed of neuroectodermal precursor cells (Medulloblastoma); common in children
Secondary: Metastatic brain tumors.
The most common primary malignant brain tumor are.
Glioblastoma is the most common primary brain tumor in adults
Medulloblastoma is the most common tumor in children

6. Topographical Classification Of CNS Tumors
Supratentorial tumors (above the tentorium cerebelli)
Common in adults
Cerebral hemispheres
Infratentorial tumors (below the tentorium cerebelli)
Brain stem and medulla
Common in children
Spinal cord tumors
Regional Classification

7. The most common sites of primary intracranial tumors

8. WHO Grading System of CNS Tumors
Grade IV
Grade III
Grade II
Grade I
a malignant tumor
grows fast
Invading the local tissue
ill-defined, edema
anaplastic tumor cells
mitosis is common
Abundant abnormal b.v.
hemorrhage and necrosis
higher cytological atypia
frequent mitosis
Usually recur
developing higher grade.
Infiltrative Tumor
increased cellularity
mild atypia
rare mitosis
developing higher grades.
a benign tumor
grows slowly
Circumscribed
well differentiated tumor
Good prognosis

9. Estimated mean-survival according to grade:
With grade 2 tumors is 5 to 10 years
With grade 3 tumor is 2 to 3 years
With grade 4 tumor is 1 to 1.5 years

10. Unique characteristic of CNS Tumors
Anatomic Site: local effects (e.g., a benign meningioma may cause cardiorespiratory arrest from compression of the medulla)
Infiltration: Even low-grade lesions may infiltrate large regions of the brain, leading to serious clinical deficits, inability to be resected, and poor prognosis
Metastasis: Even the most highly malignant gliomas rarely spread outside of the CNS
Dissemination: Brain tumors are prone to disseminate and seed along the CSF pathways
Recurrence: recurrent tumors developing higher grades
Therapy: therapeutic options are limited

11. Clinical Signs And Symptoms Caused By Brain Tumors.
Compression
Destruction
Infarction and hemorrhage
Cerebral edema
Obstruction of CSF flow
Increased intracranial pressure

12. The main reasons of intracranial hypertension caused by brain tumors
Mass effect of the tumor
Brain edema
Obstruction of the CSF and resulting hydrocephalus
Increased intracranial pressure manifested by:
Headache
Vomiting
papilloedema

13. Gliomas Gliomas, derived from glial cells, include:
The most common 1ry tumors of the brain (80% of tumors in adult)
Gliomas, derived from glial cells, include:
Astrocytomas (derived from astrocytes)
Oligodendrogliomas (derived from oligodendrocytes)
Ependymomas (derived from ependymal cells)

14. Astrocytomas
It classified into
Non infiltrating astocytoma (Pilocytic astrocytoma Grade I)
Infiltrating astrocytoma include;
Diffuse fibrillary astrocytomas (grade II).
Anaplastic astrocytoma (grade III).
Glioblastoma multiforme (grade IV)

15. Pilocytic astrocytoma (WHO grade I)
They typically occur in children and young adult (20s)
Usually located in the cerebellum
Microscopically, there are proliferating astrocytes with long, thin "hairlike" processes, rosenthal fibers and microcysts
Good prognosis

16. Gross
Is often cystic, with a mural nodule in the wall of the cyst.

17. Fibrillary (Diffuse) Astrocytoma (WHO grade II)
Usually found in the cerebral hemispheres, they may also occur in the cerebellum, brainstem, or spinal cord
Most often in the fourth through sixth decades
They remain static or progress slowly over a number of years
Eventually, clinical deterioration occurs due to the appearance of a tumor of higher histologic grade
Microscopically, there is increased number of glial cell nuclei, mild nuclear pleomorphism, fibrillary background

18. Brain, astrocytoma - Gross, coronal section
This image illustrates the gross appearance of a well-differentiated infiltrating astrocytoma, usually designated simply as astrocytoma, involving the right thalamus

19. Anaplastic astrocytomas (WHO III)
Densely cellular regions
Greater nuclear pleomorphism
Mitotically active cells
Glioblastoma multiforme (WHO IV)
Associated with very bad prognosis
Microscopically Resemble anaplastic astrocytoma with the additional features of:
Pseudopalisading necrosis)
Vascular or endothelial cell proliferation

20. Brain, glioblastoma - Gross, coronal section
The cut surface of the tumor shows areas of yellow discoloration, corresponding to areas of necrosis.
Although the lesion appears to be somewhat circumscribed grossly, this tumor widely infiltrates the adjacent brain and often crosses the corpus callosum to involve the opposite hemisphere

21. Pseudopalisading necrosis
vascular or endothelial cell proliferation.

22. Summary of Astrocytomas
Prognosis
Microscopic
Macroscopic
Location
Incidence
Types
Good prognosis
Proliferating astrocytes with hairy like process- Rosenthal fibers- microcysts
Cystic mural nodule
Common site is cerebellum
Children and young adult (20s)
Pilocytic Astrocytoma
(WHO I)
Increased grim prognosis with grade
Increase no. of cells
Mild to modertae nuclear pleomorphism
Fibrillary background
Infiltrative pattern without forming a discrete mass
Common site is
Cerebral hemispheres
80% of adults
40-60 years
Diffuse fibrillary astrocytoma
(WHO II)
Higher atypia
frequent mitosis
Anaplastic astrocytoma
(WHOIII)
Pseud palsiding necrosis
Vascular and epithelial proliferation
Appears necrotic with areas of hemorrhage
Glioblastoma multiform
(WHO IV)

23. Oligodendroglioma (WHO II/ III)
Incidence: 5% to 15% of gliomas Age: years Site: cerebral hemispheres (frontal and temporal lobe) Prognosis: Better prognosis than astrocytomas Gross: well-circumscribed, gelatinous, gray masses, often with cysts, focal hemorrhage, and calcification

24. Microscopically:
Monomorphic sheets of regular cells with spherical nuclei surrounded by a clear halo of cytoplasm (Fried Egg Appearance)
Anastomosing capillaries
Calcification

25. Ependymoma (WHO II/ III)
Incidence: Account 5- 10% of primary CNS tumors Site: Children: at the floor of ventricles Adult: at the spinal cord Age: Common in the first two decades of life, also can occurs in adults Prognosis: Most ependymomas behave as WHO grade II lesions

26. Ependymoma (WHO II/ III)
Because of the relationship of ependymomas to the ventricular system, CSF dissemination is a common (poor prognosis)
Anaplastic ependymomas (WHO grade III)
Increased cell density
high mitotic rates
areas of necrosis
less evident ependymal differentiation

27. Grossly: In the fourth ventricle, ependymomas are solid or papillary masses extending from the floor of the ventricle
Microscopically: Ependymomas are composed of cells with regular, round to oval nuclei with abundant granular chromatin on a fibrillary background
Tumor cells may form gland-like structures (Rosettes) or are arranged around blood vessels (Perivascular pseudorosettes)

28. Ependymoma. Photograph of an autopsy specimen sectioned through the level of the fourth ventricle shows a soft, friable heterogeneous mass (arrows) within the fourth ventricle. Scattered areas of hemorrhage are noted

29. Tumor cells form round or elongated structures (rosettes, canals) 
tumor cells are arranged around vessels with an intervening zone containing thin ependymal processes

30. Summary Increased grim prognosis with grade
Microscopic
Macroscopic
Location
Incidence
Types
Increased grim prognosis with grade
- Monomorphic cells with fried egg appearance.
Anastmosing capillaries and
calcification.
Anaplastic oligodendrogliomas
Showing higher pleomorphism and frequent mitosis.
infiltrating gelatinous tumor with areas of calcifications and hemorrhage
Cerebral hemispheres
5-15% occurs in adult years
Oligodendrogliomas (WHO II/ III)
Cells with round regular nuclei forming rosettes and perivascular pseudorosettes.
Anaplastic ependymoma showing increased cellularity and frequent mitosis and necrosis.
Solid or papillary mass
In young occurs at the ventricular system
In adult common in spinal cord
5-15%
Occurs in the first 2 decades and adults
Ependymoma (WHO II/ III)