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

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

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.

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

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

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

The most common sites of primary intracranial tumors

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

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

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

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

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

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)

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)

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

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

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

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

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

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

Pseudopalisading necrosis vascular or endothelial cell proliferation.

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)

Oligodendroglioma (WHO II/ III) Incidence: 5% to 15% of gliomas Age: 40- 50 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

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

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

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

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)

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

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

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 40-60 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)