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ROLE OF CSF IN TUMORS OF THE BRAIN
Introduction
Cerebrospinal fluid
CSF is plasma ultra filtrate, forming from choroid plexuses, entering the subarachnoid space through the foramina of luschka and magendie, circulating upward over the cerebral hemisphere as well as downward over the spinal cord and entering the venous blood through arachnoid villi of the dural sinuses. CSF is formed by both active secretions in the choroid plexus and diffusion from plasma. Although absorption is chiefly by arachnoids villi into dural sinuses they appears to be same absorption by pal capillaries and spinal nerve roots.
Solute concentrations in CFS resemble cerebral extracellular fluid and this makes it important in diagnosis of various disease conditions.
To obtain CFS
CSF for cytology and other clinical use is usually obtained through lumbar puncture at position L4-L5.The CSF can also be obtained from cerebral ventricles and cisterns (occasionally)
Other than for obtaining CSF lumbar puncture can be used for:
1. Introduction of radiographic contrast material
2. Electrolyte disturbance evaluation
3. Lower intracranial pressure
4. Removal of exudation or blood from sub site of puncture
The role of csf cytology in diagnosis of the cns tumors
Cytological examination of CFS is the important tool for diagnosis of tumors and response of tumors to therapy. Although the finding of exfoliated malignant cells in the CFS is a graver prognosis, it frequently helps to indicate more appropriate therapy.
In general intracranial tumors vascular and degenerative disease and inflammatory conditions of CNS tissue is not obviously detectable by exfoliative cytological CFS evaluating due to lack of communication with leptomeninges ling cells and free flowing CFS. However exfoliation of malignant cells into the csf depends on the cohesiveness of the tumor cells.
Demonstration of cancer cells in spinal fluid is the basis of using csf as the diagnostic tool in the CNS tumors. The method has proved very useful in clarifying obscure neurological situations in patients suspected of harboring cancer metastatic to the CNS particularly leukemia. It’s also useful in evaluation of primary tumors.
An obvious condition for successful cytologic diagnosis is the seeding of tumor cells into the subarachnoid space or the cerebral ventricles. This condition is fulfilled only in a comparatively small percentage of cases. Even if the lesion is in contact with the csf the number of malignant cells observed is small.
The diagnosis rests on presence of dozen or sometimes fewer malignant cells. However in this particular setting a single abnormal malignant cell must be carefully evaluated.
The presence of extensively abundant cancer cells shows extensive involvement of leptomeninges.
Tumors of the CNS
Tumors of the brain can either be metastatic or primary originating from the CNS cells
a. Metastatic
Leukemia and malignant lymphomas are the most frequent and may be having high frequency than quoted among the numerous metastases that can be found in the brain.
The finding of single leukemic cells in the csf of leukemic patients is far meaninglessly unless there is clinical symptomatology suggestive of involvement of CNS. On the other hand, the finding of numerous leukemia cells is indicative of strong involvement of subarachnoid space. The same applies to malignant lymphoma.
Such cells are critically identified.
Picture
A
Recognizable cancer cells in the CSF; mammary carcinoma
Meduloblastoma
Distorted easily recognizable malignant cells in the CSF
Melanoma in subarachnoid space: Many cells
Metastatic epithelial tumors
Metastatic bronchogenic and mammary carcinomas and occasionally other malignant neoplasm as well may be identified in CSF. The malignant cells usually occur singly or in small clusters and are sparse. The occurrence of numerous cells suggests involvement of the subarachnoid space. The malignant cells are largely accompanied by large histeocytes
With histeocytes
With hemosiderin
The number of histeocytes may increase after treatment by radiation or chemotherapy.
Because there are virtually no cells in normal CSF that could be confused with cancer cells, even the presence of a very few cells with clear evident nuclei abnormality is of great diagnostic importance in this medium.
Primary Tumor
CSF cytology is of less importance in primary than in metastatic tumors. Only 25% of primary CNS tumors shed identifiable cells into the CSF. The fluid from ventricles and cistern magna is of important/value than lumbar tap
Recognition of cells originating in the primary neoplasm of the CNS in CFS depends on two factors
• Anatomic degrees
• Degree of differentiation
Tumors located within the depth of the brain or the spinal cord can not be recognized since they are not bathed by CFS. Well differentiated glial tumors (astrocytoma 1&2) do not shed ready cells when compared to poor differentiated tumors such as (astrocytoma 3&4).Furthermore, the recognition of the cells from well differentiated neoplasm fraught with difficulties as these tumors are made from cells with benign appearance e.g. cells from ependymoma appear as benign caboidal or columnar cells.
The recognition of the tumors lies in the finding of foreign cells in CSF. For instance:
1. Low grade astrocytoma (Grade 1&2 ).They shed very few cells into the CFS, the cells appear epithelial, although occasionally stallate cytoplasm may be observed .The nuclear appears pale not enlarged and cannot be recognized as malignant.
2. High grade astrocytoma 3&4 (Glioblastoma multiforme).The CSF may contain a few cells with Nuclear enlargement and hyperchromasia multinucleated giant cells, so characteristics of this tumor in tissue are very rarely seen in CFS. The presence of conspicuous cancer cells in CFS in much more likely to represent a metastatic tumor than a high grade glioma
3. Oligodendroglioma
Made up of uniformly round cells with round and eccentric nuclei
4. Midline tumors
This large group of tumors of diverse origin and histological presentation occupy the area surrounding the midbrain (diencephalon).The group include tumors of pituitary, the pineal cord and craniopharyngiomas. The tumors are readily accessible to an aspiration biopsy and except for malignant tumors of pineal region are very rarely recognized in CFS. Tumors of pineal region may be benign as well as malignant. They occur in several forms as benign or malignant pineolomas, benign dermoid cysts, malignant pineolomas, malignant teratomas and germinomas.
Germinomas which occurs predominantly in young boys are recognized in CFS.
Meduloblastoma is a highly malignant small cell neoplasm often invading the subarachnoid space. Cytologicaly, the cells of meduloblastoma can not be differentiated from cells of histologically similar tumors such as neuroblastoma or retinoblastoma. Normally the cells have customary appearance of malignant cells in fluids. No abnormal cells are seen in meningiomas unlike in meningeal sarcoma.
Other parameters apart of CSF in tumor diagnosis include.
There are tumor makers in csf:
• fetoprotein in CNS dysgerninomas meningeal carcinomatosis
• Beta glucoronidase possibly in meningeal carcinomatosis
• carcinombryonic antigen CEA meningeal carcinomatosis, intradural or extradural or brain parenchymal metastasis from adenocarcinoma.
• Human chorionic gonadotropin HCG, CNS dysgerninomas and meningeal carcinomatosis.
The disadvantages of using CSF cytology to diagnose CNS tumors include;
1. It cannot be used to diagnose all CNS tumors as some tumors are not easily reflected in the CSF as discussed above
2. It is not precise as it is difficult to differentiate some malignant cells in CSF
3. It is expensive as it requires specialists and special equipments
4. It is dangerous especially when obtaining the CSF
Dangers
i. -production of cerebella pressure cone in patients with increased intracranial pressure
ii. -introduction of infection by passing needle through superficial or deep sepsis in the region
iii. -chronic back pain
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