• Glioblatomas are either:1. Primary- The patients develop it from the start- Is the most common type of glioblastoma2. Secondary- Progress from lower gradesNote : Once the histologic features of glioblastoma

appear, the prognosis is very poor; with treatment( resection , radiotherapy , and chemotherapy), the median survival is only 15 months

• Note: Infatile pilocytic astrocytoma is called pilomyxoid astrocytoma and it is grade II typically located in the hypothalamus

Morphology of pilocytic astrocytomaGross:- Well circumscribed- Is often cystic, with a mural nodule in the wall of

the cyst

- Tumors that appear on MRI as cyst containing a nodule are:

a. Pilocytic astrocytomab. Gangliogliomac. Pleomorphic Xantho astrocytoma

Microscopically, pilocytic astrocytoma- The tumor showsa. Hypercellular areas composed of bipolar

astrocytes with with long, thin "hairlike " processes that are GFAP positive

b. Hypocellular areas formed of microcysts. c. Rosenthal fibers d. Eosinophilic granular bodies, e. Necrosis and mitoses are absent.• Genetically Pilocytic astrocytomas don’t show

mutations in IDH1 and IDH2

Pilocytic astrocytoma

Pilocytic astrocytoma

B. Oligodendroglioma - These tumors constitute about 5% to 15% of

gliomas- Are most common in the fourth and fifth decades. - Patients may have had several years of neurologic

complaints, often including seizures. - The lesions are found mostly in the cerebral

hemispheres, mainly in the frontal or temporal lobes

- Patients have better prognosis than astrocytomas of similar grade

MorphologyGross- Are infiltrative tumors - may show cysts, hemorrhage, and calcification.Note: Is the most common CNS tumor showing

calcificationOn microscopic examination, 1. Grade II oligodendroglioma: - Is composed of sheets of regular cells with

spherical nuclei containing fine chromatin- The nuclei are surrounded by a clear halo of

cytoplasm

Grade II oligodendroglioma

- The tumor typically contains a delicate network of anastomosing capillaries.

- Calcification, present in as many as 90% of these tumors,

2. Grade III anaplastic oligodendroglioma- Characterized by:a. Significant mitotic activity(minimum criterion)b. And/or microvascular proliferationc. And/ or necrosis(geographic or

pseudopalisading)

- Treatment with surgery, chemtherapy , and radiotherapy yield an average survival of 10-20 years for grade II and 5-10 years for grade III.

- The most common genetic findings in oligodendrogliomas is 1p19q codeletion

- Tumors with just those specific changes have a consistent and long-lasting response to chemotherapy

C. Ependymoma - Ependymomas most often arise next to the

ependyma-lined ventricular system, including the central canal of the spinal cord.

- In the first two decades of lifea., they typically arise from floor of the fourth ventricle b. and constitute 5% to 10% of the primary brain

tumors in this age group. - In adults,- the spinal cord is their most common location; and

is considered as the most common type of glioma in the spinal cord in adults

- tumors in this site (if multiple) are particularly frequent in the setting of neurofibromatosis type 2

Notes- May arise in the supratentorial region- The clinical outcome for completely resected

supratentorial and spinal ependymomas is better than for those in the posterior fossa

Microscopically:1. Grade II ependymomas- Are well circumscribed gliomas - Composed of cells with regular, round to oval

nuclei - Between the nuclei there is a variably dense

fibrillary background- Tumor cells may form:1. Round or elongated structures ( True rosettes,

canals) that resemble the embryologic ependymal canal with long, delicate processes extending into a lumen

True Rosettes of ependymoma

- Are specific to ependymoma- but are infrequent2. Perivascular pseudo-rosettes - More frequently present - Not specific to ependymomas - Tumor cells are arranged around vessels with an

intervening zone containing the ependymal processes

.

Ependymoma

Perivascular pseudo rosettes

2. Anaplastic ependymomas (grade III) show :- Microvascular proliferation- Pseudopalisading necrosisNote:- Presence of geographic necrosis can be seen

in grade II ependymomas and doesnt upgrade

3. Myxopapilllary ependymoma ( grade I ) - Arises in the filum terminale - and has good prognosis but tends to recur if not

completely excised

II. Neuronal Tumors 1. Central neurocytoma (grade II)- Is a low-grade neuronal neoplasm - Found within and adjacent to the ventricular

system (most commonly at the level of foramen of Munro)

2. Gangliogliomas- Are tumors with a mixture of glial elements

(looking like a low-grade astrocytoma) and mature-appearing neurons.

- Most of these tumors are slowly growing,

- These lesions often present with seizures

Embryonal primitive neoplasms - The most common is the medulloblastoma,

accounting for 20% of pediatric brain tumors. Medulloblastoma (WHO grade IV)- occurs predominantly in children - and exclusively in the cerebellum. - The tumor is highly malignant, - The prognosis for untreated patients is dismal - It is radiosensitive- With total excision and radiation, the 5-year

survival rate may be as high as 75%.

.- Tumors of similar histology can be found

elsewhere in the nervous system (called CNS primitive neuroectodermal tumor, or CNS PNET )

Morphology- In children, medulloblastomas are located in the

midline of the cerebellum (vermis) but may extend to the surface of the cerebellar folia and involving the leptomeninges

- Lateral tumors (in cerebellar hemispheres) occur more often in adults.

Microscopicallya. Are extremely cellular, with sheets of anaplastic

("small blue") cells b. Individual tumor cells are small, with little

cytoplasm and hyperchromatic nuclei; c. Mitoses are abundant. d. May show Homer-wright rosettes as evidence of

neuronal differentiation

Medulloblastoma

medulloblastoma

IV. Primary Central Nervous System Lymphoma - Accounts for 1% of intracranial tumors.A- It is the most common CNS neoplasm in

immunosuppressed individuals (including transplant recipients and persons with AIDS); under these circumstances the CNS lymphomas are nearly all driven by Epstein-Barr virus and show necrosis

B. In non-immunosuppressed populations, the age spectrum is relatively wide, with the incidence increasing after 60 years of age;

- Most of these tumors are diffuse large B-cell lymphomas

- Regardless of the clinical context, primary brain lymphoma is an aggressive disease with relatively poor response to chemotherapy as compared with peripheral lymphomas

- Individuals with primary brain lymphoma often have multiple sites of tumor within the brain parenchyma;

-. Lymphoma arising outside the CNS rarely involves the brain parenchyma; when it does occur, there is usually tumor within the CSF and around intradural nerve roots

-

V. Germ cell tumors- Primary brain germ-cell tumors occur commonly in:A. Pineal regionB. suprasellar region- 90% occur during the first two decades of life- CNS involvement by a gonadal germ-cell tumor is

not uncommon

VI. Meningiomas : - They occur in adults - Are predominantly benign tumors that arise from

arachnoid cap cells and attached to the dura.- May be found along any of the external surfaces of

the brain as well as within the ventricular system, where they arise from the arachnoid cells of the choroid plexus.

- Clinically they either present with vague non-localizing symptoms, or with focal findings referable to compression of adjacent brain.

- Although most meningiomas are easily separable from underlying brain, some may infiltrate the brain, a feature that is associated with an increased risk of recurrence

- The overall prognosis is determined by the location, surgical accessibility, and histologic grade.

- When a person has multiple meningiomas,with bilateral vestibular schwannomas or spinal ependymoma, the diagnosis of NF2 syndrome should be considered

- About half of meningiomas not associated with NF2 have acquired loss-of-function mutations in the NF2 tumor suppressor gene on the long arm of chromosome 22 .

- These mutations are found in all grades of meningioma,.

- NF2 mutations are more common in tumors of certain patterns (fibroblastic, transitional, psammomatous).

Gross-: WHO grade I grow as well-defined dura-based

masses that may compress the brain but do not invade it and extension into the overlying bone may be present and does not upgrade the tumor to grade II.

Microscopic : - Oval cells with indistinct borders and - Intranuclear pseudoinclusions - arranged in syncytia with whorling

Meningioma

Meningeoma

Grade I- No more than 3 MF/10HPF 2. Grade II meningeoma are recognized by either:A. Mitotic figures of more than 3 but less than 20 per 10

HPF(high power fields)B. Or presence of 3 of the following 5 atypical features1. Small cells, 2. Prominent nucleoli ,3. Sheeting4. Hypercellularity, 5. Spontaneous necrosis not induced by embolization

C. Or Brain invasionD. Clear or chordoid variants- These tumors are more aggressive with a higher rate of

recurrence and may require radiation therapy in addition to surgery

3. Anaplastic (malignant) meningiomas (WHO grade III) - Are highly aggressive tumors characterized by either:a. They resemble a high-grade sarcoma or carcinoma or

melanomab. Or Mitotic figures of 20 or more per 10HPF(high power

fields)c. Papillary or rhabdoid variants

VII. Metastatic Tumors - The most common primary sites are lung, breast,

skin (melanoma), kidney, and gastrointestinal tract-- Metastases form sharply demarcated masses, often

at the gray-white junction, and elicit marked edema - The boundary between tumor and brain parenchyma

is sharp at the microscopic level as well

CNS manifestaions of Familial Tumor SyndromesI. Tuberous Sclerosis :- Is an autosomal dominant

syndrome characterized by a. The development of CNS hamartomas consist of:

Cortical tubers which are associated with seizures and can be difficult to control with antiepileptic drugs.

b. Benign brain neoplasms such as subependymal giant cell astrocytoma and because of their proximity to the

foramen of Monro, they present acutely with obstructive hydrocephalus, which requires surgical intervention

2. von Hippel-Lindau Disease: - An autosomal dominant- The CNS tumor is hemangioblastoma (grade I)

Hemangioblastomas insporadic cases occur in the cerebellar hemispheres and spinal cord

In von Hippel-Lindau Disease: , tend to occur as multiple lesions in the spinal cord

Paraneoplastic syndromes affecting the brain 1. Subacute cerebellar degeneration - Resulting in ataxia, with destruction of Purkinje

cells, 2. Limbic encephalitis :- Causing a subacute dementia, - Charcterized by perivascular inflammatory cells,

some neuronal loss, and gliosis, in the medial temporal lobe

3. Syndrome of rapid-onset psychosis, epilepsy, and coma

- Associated with ovarian teratoma and antibodies against the N-methyl-d-aspartate (NMDA) receptor