| How is histology of nervous system? | ➢ Composed of neurones, neuronal processes, supporting cells of the CNS (glial cells) and blood vessels.
➢ Suspended with meninges and containing fluid, the cerebrospinal fluid (CSF) which is produced by specialised choroid plexus structures.
➢ Consists of a vast number of neurones and their processes embedded in a mass of support cells, collectively known as neuroglia, which form almost half of the total mass of the CNS.
➢ These are highly branched cells that occupy the spaces between neurones; they have intimate functional relationships with the neurones, providing both mechanical and metabolic support |
| What is amyloid angiopathy? | non neoplastic lesion
➢Marked thickening with a pink hyaline appearance of small peripheral cerebral artery
➢Leakage of red blood cells
➢The amorphous pink amyloid has
weakened the vascular walls to allow either “microbleeds” or more extensive lobar hemorrhage |
| What is acute meningitis? | non neoplastic lesion
➢ Prominent dilated vessels
➢ Edema and focal inflammation
➢ This acute meningitis is typical of a bacterial infection.
➢ Edema can lead to brain swelling with herniation and death.
➢ Resolution of infection may be followed by adhesive arachnoiditis with obliteration of the subarachnoid space leading to obstructive hydrocephalus.
➢ Diagnosis is reached by performing lumbar puncture to obtain CSF that typically shows increased leukocytes, mainly neutrophils, decreased glucose, and increased protein.
➢ Gram stain, serologies, and culture help identify specific microorganisms |
| What are abscesses? | The acute inflammatory cells in the abscess with adjacent cerebral cortex. Note the prominent small artery with thickened wall and dilated lumen, which imparts the ring enhancement visible with radiologic scans. |
| What rae general remarks regarding NCS tumors? | ➢The annual incidence of CNS tumors ranges from 10 to 17 per 100,000 Individuals for intracranial tumors
➢ Tumors of the CNS account for as many of 20% of all pediatric tumors.
➢Childhood CNS tumors differ from those in adults in both histologic subtype and location ( In childhood: tumors are likely to arise in the posterior fossa, whereas tumors in adults are mostly supratentorial).
➢Tumors of the nervous system have unique characteristics that set them apart from neoplastic processes elsewhere in the body.
• They do not have morphologically evident premalignant or in situ stages comparable to those of carcinomas.
• Even low-grade lesions may infiltrate large regions of the brain, leading to serious clinical deficits, inability to be resected, and poor prognosis.
• The anatomic site of the neoplasm can influence outcome independent of histologic classification due to local effects
• Even the most highly malignant gliomas rarely spread outside of the CNS. |
| What is histologic classification of CNS tumros? | I. Intracranial secondary Tumors = métastasis
II. Intracranial primitive Tumors :
➢ Gliomas
➢ Ependymal Tumor
➢ Choroïd plexus tumors
➢ Neuronal et glio-neuronal Tumors
➢ Méningiomas
➢ Primary brain tumors from non nervous origin
➢ Primary brain tumors from non nervous origin :
Germinal tumors
Lymphomas
Mélanocytic Tumors
Craniopharyngioma
Pituitary Adenomas |
| What are astrocytic and oligodendrocytic gliomas? high grade and low grade gliomas? | ➢ Defined by the type of tumor cell and by the histological grade: histological aspects correlated with less differentiation and greater aggressiveness.
➢The grade follows the WHO classification : from grade I to grade IV
➢ Anaplasia (malignant transformation of the tumor) characterizes a highgrade tumor
➢We contrast circumscribed Gliomas which are usually benign (grade I)
to infiltrating gliomas which can be either low grade (II) or high grade (malignant: grade III and IV).
➢ The most common circumscribed glioma is Pilocytic astrocytoma; it occurs in children |
| What is pilocytic astrocytoma? | ➢ Typically affect children and young adults.
➢ Most commonly located in the cerebellum, they also may involve the third ventricle, the optic pathways, the spinal cord, and occasionally the cerebral hemispheres
➢ Relatively benign tumors
➢ Have a very good prognosis after surgical removal.
➢These are often slow-growing, low-grade astrocytic tumors that are minimally infiltrative
➢ On MRI, the the typical appearance of a pilocytic astrocytoma is that of a large cerebellar cyst with a small mural nodule
➢ Pilocytic cells with long thin processes that are GFAP positive, similar to cells of other gliomas, Red Rosenthal fibers
➢ Tumor cells often contain Rosenthal fibers and eosinophilic granular bodies.
➢ PAs are highly vascular and enhance with contrast injection. Most PAs are biologically low grade and do not evolve into more malignant tumors.
➢ Surgical excision of cerebellar PA (even partial resection in some instances) sometimes results in permanent cure |
| What are infiltrative/diffuse gliomas? | ➢ Preferentially affect the cerebral hemispheres
➢ Whatever their initial grade, they progress inexorably towards higher grade lesions.
➢On the basis of histologic features, astrocytomas are stratified into three groups: diffuse astrocytoma (grade II), anaplastic astrocytoma (grade III), and glioblastoma (grade IV), with increasingly grim prognosis as the grade increases.
➢ These lesions do not metastasize to other organs such as the liver or lungs
➢ They can exceptionally give intra-axial metastases (intrarachidian dissemination in the CSF) or along the peripheral nerves.
➢The identification of certain molecular alterations makes it possible to better define the tumor process and its prognosis |
| How is diffuse astrocytoma? | ➢A diffuse fibrillary astrocytoma is a form of glioma that is lower grade and not as extensively invasive as a glioblastoma.
➢ Account for about 80% of adult gliomas
➢They are most frequent in the fourth through the sixth decade
➢ usually are found in the cerebral hemispheres.
➢ Tend to enhance brightly because of their abnormal vascularity.
➢ This astrocytoma shows increased cellularity and pleomorphism compared with normal brain, but far less than a high-grade glioma.
➢ The clinical course may be slowly progressive for years, but astrocytomas have a tendency to become more anaplastic with time as genetic alterations accumulate within the neoplastic cells, and then more rapid deterioration ensues |
| What is oligoderndroglioma? | ➢ Account for 5% to 15% of gliomas and most commonly are detected in the fourth and fifth decades of life
➢ MRI image shows a mass usually well circumscribed, with cystic areas and focal calcification.
➢ It enhances as a result of the rich vascular network of anastomosing capillaries within the tumor.
➢They typically occur within the cerebral hemispheres, usually in white matter, of adults in their 30s and 40s.
➢ Typical oligodendrogliomas have round blue nuclei with clear cytoplasm (WHO II)
➢ Most have cytogenetic abnormalities involving chromosomes 1p and 19q.
➢ They tend to be slowly progressive over years and can have a better prognosis than other adult gliomas |
| What is glioblastoma? | ➢Gliomas account for more than 80% of all primary brain tumors in adults.
➢Most are located above the tentorium and within the cerebral hemispheres.
➢ GB are poorly circumscribed, large masses and have extensive necrosis
➢ Patients may initially have a new-onset seizure disorder, headaches, or focal neurologic deficits.
➢Although this neoplasm is highly aggressive within the brain, metastases outside the CNS are rare.
➢ IDH Wildtype!!! |
| How is morphology of glioblastoma? | ➢ T2-weighted MRI image in axial view shows a large infiltrative mass
➢ With central necrosis, edema, and an irregular border.
➢ For not resectable, radiation and chemotherapy may add months to patient survival.
➢ Gliomas may begin as low-grade neoplasms that often have TP53 mutations, and as they progress to higher-grade lesions
➢ Highly cellular neoplasm with marked hyperchromatism and pleomorphism.
➢ Prominent vascularity and area of pale necrosis with neoplastic cells concentrated around it.
➢ Pseudopalisading necrosis is characteristic of glioblastoma.
➢The cells can infiltrate widely, particularly along white matter tracts, and even through the
CSF.
➢Such highly anaplastic cells may be difficult to differentiate from metastases, but gliomas
should be GFAP positive with immunohistochemistry. |
| What are ependymal and choroid plexus tumors? | I - Ependymal Tumors :
➢ependymoma (grade II) ;
➢Anaplastic épendymoma (grade III).
II – choroid plexus tumors :
➢papilloma (grade I) ;
➢Atypical papilloma (grade II) ;
➢Carcinoma (grade III).
These tumors can cause hydrocephalus resulting from the obstruction by the
tumor of the CSF flow pathways.
More rarely, they can cause hypersecretion of CSF |
| What is ependymoma? | ➢ Bright mass with cystic areas fills the fourth ventricle (most common site of an ependymoma in children).
➢ This neoplasm arises from the ependymal lining cells.
➢ Enlargement of the tumor with blockage of the CSF flow in the fourth ventricle may produce obstructive (noncommunicating) hydrocephalus.
➢Although ependymomas tend not to be invasive, they can be close to vital brain stem structures, and they can spread into the CSF and can be difficult to eradicate.
➢In adults, most ependymomas are found within the spinal cord, and some are associated with neurofibromatosis type 2
➢ The microscopic appearance of an ependymoma from the fourth ventricle reveals a rosette pattern with the tumor cells arranged around a central vascular space (perivascular pseudorosette).
➢ The ependymal processes stain positively for GFAP.
➢ A particular variety : myxo- papillary ependymoma typically arises in the filum terminale of the spinal cord of an adult.
➢The cuboidal tumor cells are arranged around papillations that have a myxoid connective tissue core. |
| What are neuronal and glio-neuronal tumors? | Far less frequent than gliomas
Composed of cells with neuronal characteristics
Typically lower-grade lesions that often present with seizures.
While some neuronal differentiation can be observed in many tumors, lesions in this group are primarily composed of cells that express neuronal markers, such as synaptophysin and neurofilaments.
Central neurocytoma :
is a low-grade neoplasm found within and adjacent to the ventricular system (most commonly the lateral or third ventricle);
it is characterized by evenly spaced, round, uniform nuclei and often islands of neuropil |
| What are menigioma? | ➢ Usually meningiomas, beneath the dura, compresse the underlying cerebral hemisphere.
➢Most often benign
➢ Represent 20% of primary barin tumors
➢Peak frequency around 5th decade
➢These neoplasms arise from meningothelial arachnoid cap cells
➢ They are typically well-circumscribed masses that are amenable to resection.
➢Sometimes they produce a flattened mass, and sometimes the overlying bone shows hyperostosis.
➢Rarely, meningiomas can be more atypical and recur, or aggressive (anaplastic) and invade the underlying brain
Predisposing factos (genetics and ionizing radiation)
➢WHO distinguishes three prognostic grades of meningiomas, with several histological variants for each grade:
● grade I meningioma (benign)
● atypical meningioma (grade II)
● malignant meningioma (grade III)T |
| How is morphology of meningioma? | ➢ Exhibit many different microscopic patterns.
➢ Most commonly the cells arrange in a tight, whorled pattern, with oval nuclei containing
dispersed chromatin, giving them an open and vesicular appearance.
➢ They may also contain psammoma bodies or fibroblastic elements.
➢ Some meningiomas, particularly when multiple, occur with neurofibromatosis 2
➢ Sporadic meningiomas often have a mutation involving the NF2 gene on the 22q chromosome.
➢ Atypical meningiomas have a higher mitotic index, increased cellularity, and increased nuclear tocytoplasmic ratio; (WHO grade II)
➢ they are associated with local invasion and increased risk for recurrence after resection.
Meningiomas are uncommon in children.
➢Anaplastic (malignant) meningiomas (WHO grade III) are highly aggressive tumors that may resemble a high-grade sarcoma or carcinoma morphologically.
➢The female-male ratio is 3:2. |
| What are other primary CNS tumors? | 1. Germinal tumors
2. Lymphomas
3. Mélanocytic Tumors
4. Craniopharyngioma
5. Pituitary Adenomas |
| What is primary CNS lymphoma? | ➢ occurs mostly as diffuse large B-cell lymphomas
➢ accounts for 2% of extranodal lymphomas and 1% of intracranial tumors.
➢ It is the most common CNS neoplasm in immunosuppressed individuals
➢ In nonimmunosuppressed populations, the age spectrum is relatively
wide, with the incidence increasing after 60 years of age.
➢ aggressive disease with a relatively poor response to chemotherapy as compared with peripheral lymphomas.
➢ often multiple tumor nodules within the brain parenchyma, in perivenytricular areas; yet involvement of sites outside of the CNS is uncommon.
➢ Conversely, lymphoma originating outside the CNS rarely spreads to the brain parenchyma |
| What is primary germ cell tumors? | ➢occur along the midline, most commonly in the pineal and the suprasellar regions.
➢They account for 0.2% to 1% of brain tumors in individuals of European descent but in as many as 10% of brain tumors in individuals of Japanese ethnicity.
➢They are a tumor of the young, with 90% occurring during the first 2 decades of life.
➢ Germ cell tumors in the pineal region show a strong male predominance.
➢The most common primary CNS germ cell tumor is germinoma, a tumor that closely resembles testicular seminoma.
➢The positivity of one or two markers (AFP or HCG ) in the blood or the CSF has a definite positive diagnostic value.
➢ For non-secreting tumors, initial histological evidence is essential to clarify the diagnosis |
| What is craniopharyngioma? | ➢Embryonic tissue defect that appeared before birth in the pituitary region.
➢ The tumor is epithelial, benign, often cystic and calcified.
➢It develops from the remains of Rathke's pocket, in and above the pituitary gland |
| What are intracranial tumors in children? | ➢Intracranial tumors are the most frequent solid tumors of the child
➢occupy the second position of the malignant affections of the child after the
➢There is a peak frequency between 4 and 8 years.
➢Infratentorial locations are by far the most frequent, except when occurring in the first weeks where supratentorial topographies predominate.
➢On the supratentorial level, the most frequent histological types are gliomas, ependymomas, craniopharyngioma.
➢The most common tumors at the sub-tentorial level are pilocytic astrocytoma (low-grade glial tumor) and medulloblastoma. |
| What is medulloblastoma? | ➢ Usually presents as an irregular posterior fossa mass arising near the midline of the cerebellum
➢ May extend into the fourth ventricle above the brain stem.
➢It is one of the small round blue cell tumors that most often occur in children.
➢These highly malignant, poorly differentiated tumors commonly spread into the subarachnoid space and seed by the CSF into the spinal canal.
➢Those associated with mutations in the WNT signaling pathway have the best prognosis.
➢ Medulloblastomas are of neuroectodermal origin and occur in the cerebellar vermis in children, where they can occlude the fourth ventricle to cause hydrocephalus.
➢ In older patients, these tumors more commonly arise within the cerebellar hemispheres.
➢These primitive tumors are very radiosensitive.
➢About a third of medulloblastomas occur in patients 15 to 35 years old.
➢Two thirds are found in patients younger than 15 years |
| How is medulloblatoma morphology? | ➢Poorly differentiated round blue cells with scant cytoplasm and hyperchromatic nuclei are shown.
➢On occasion the cells form pseudorosettes called Homer Wright rosettes with cells surrounding eosinophilic circular zones.
➢The nodular desmoplastic variant has areas of stromal response with “pale islands” that have more neuropil and show greater expression of neuronal markers.
➢The large cell variant has large irregular vesicular nuclei, prominent nucleoli, and frequent mitoses |
| What are CNS tumors initial clinical settings? | Four main circumstances can reveal an intracranial tumor:
➢Intracranial hypertension syndrome
➢Comitia crises
➢More or less rapidly progressive focal neurological deficits
➢Psychiatric disorders.
➢In the case of pituitary adenoma, endocrine signs and visual disturbances
(bitemporal hemianopsia) are in the foreground
➢The diagnosis is suspected on imaging data with and without injection of contrast medium (CT / MRI) but can only be confirmed by histological examination of stereotaxic brain biopsies or a piece of excision of the lesion |
| How is metastasis in CNS tumors? | ➢ Most common cause of brain tumors in adults.
➢ Most often multiple (in 75% of cases).
➢ They originate from primary bronchopulmonary cancer in 30% of cases and
mammary cancer in 25% of cases.
➢ When brain metastases are the first sign revealing a neoplastic process, the
primary tumor is very often a bronchopulmonary cancer.
➢ More rarely, it can be a melanoma, a renal or digestive carcinoma.
➢ Metastases from a known primary cancer in progression (with histological evidence) are generally not biopsied. |
| How does metastasis occur? | ➢ In the absence of a known primary tumor, a histological examination is necessary (on the most accessible lesion: on the primary lesion if it is found, another metastatic site or on the brain biopsy).
➢ The study of stereotaxic brain biopsies or a metastasectomy allows in most cases to find or orient the clinician towards the primary tumor.
➢ This will be done based on architectural, cytological aspects, and especially the immunoprofile.
➢ It may happen (around 10% of cases) that the primitive is not found. They are generally so-called adenocarcinomas then from unknown primary |
