Brain Tumors Lecture Notes PDF

‫بسم اهلل الرحمن الرحيم‬ Brain Tumors Dr. Ahmed Almobarak  Lecture outlines 1. The intended learning outcomes. 2. General characteristics of CNS tumors. 3. Clinical features of CNS tumors 4. WHO Classification of CNS tumors. 5. The most common tumors of CNS: epidemiology,...

‫بسم اهلل الرحمن الرحيم‬ Brain Tumors Dr. Ahmed Almobarak  Lecture outlines 1. The intended learning outcomes. 2. General characteristics of CNS tumors. 3. Clinical features of CNS tumors 4. WHO Classification of CNS tumors. 5. The most common tumors of CNS: epidemiology, morphology, pathogenesis, genetics.  The intended learning outcomes By the end of this lecture, the student is expected to be able to: 1. List the most common tumors of the CNS: according to WHO classification. 2. Explain the most important clinical features. 3. Describe the main morphological features of CNS tumors. 4. Describe the main genetic mutations in CNS tumors.  Introduction I Tumors of the central nervous system (CNS) are a diverse group of neoplasms That can arise from any of the cell types within the brain, spinal cord, or meninges. These tumors can be primary, originating from the CNS itself, or secondary, resulting from metastasis of cancers from other parts of the body.  Introduction II Estimated incidence of brain tumors 5–20 /100,000 population. All ages are affected but with two distinct peaks, one in childhood (3 - 12 years) and another in adults (55 to 65 years). CNS tumors represents about 20% of childhood cancers (2nd after leukemia).  Introduction III Childhood CNS tumors differ from those in adults in both histologic subtype and location. Childhood tumors are usually sub tentorial while in adults tumors are supra tentorial. ¼- ½ of brain tumor are metastatic tumors.  Introduction IV CNS tumors vary widely in their behavior, from benign growths to highly malignant cancers. They represent a significant cause of morbidity and mortality due to their critical location, which can affect vital neurological functions even if the tumors are histologically benign  Primary brain tumor These are brain tumor that arise from cells that are intrinsic to CNS or it is coverings. Characterize by the following: They do not have detectable premalignant or in situ stages. Even low-grade lesions are infiltrative tumors, some times affecting large areas of the brain. The course of patient is influenced by patterns of growth and anatomical location. They rarely spread outside of the CNS; they infiltrate locally or reach the subarachnoid space causing multiple implants in brain or spinal cord.  Etiology and pathogenesis 1- Genetic factors: A- Mutations in isocitrate dehydrogenase (IDH) genes occur in grade II astrocytomas and oligodendrogliomas. These mutations may occur in IDH1 or IDH2 and lead to increased production of 2-hydroxyglutarate, which interferes with the activity of several enzymes that regulate gene expression. B- Mutations in the promoter for telomerase, which contribute to the immortalization of tumor cells. C- P53 mutations.  Genetic factors continue… Co-deletion of 1p and 19q chromosomal segments are present in oligodendrogliomas. Overexpression of the platelet-derived growth factors in GII astrocytoma. Inherited genetic mutations: brain tumors are major component of several autosomal dominant disorders (neurofibromatosis, tuberous sclerosis and von Hippel Lindau syndrome).  Risk factors … continue 2- Radiation: e.g. Meningioma. 3- Immunosuppression: primary CNS lymphoma in HIV patients.  Pathology Tumors of the brain produce neurologic feature by: 1. Tumor directly invade, infiltrate and damage brain tissue disturbing function. 2. The growth of intra-cranial tumors with accompanying edema+ new blood vessels  raised intra-cranial pressure impair blood supply,.. herniation. 3. Tumors proximal and/or close to the ventricles may obstruct the flow of cerebrospinal fluid, leading to hydrocephalus.  Diagnosis 1- Clinical features: patient age, gender, neurological features. 2- Radiological diagnosis; Imaging studies: X ray. MRI and CT scan. 3- Laboratory diagnosis: - Biopsy. - Genetic studies.  Clinical features of brain tumors Even small brain tumor causes symptoms. 1- Symptoms of increase intracranial pressure (Headache, vomiting, blurred vision… etc. 2- Convulsions. 3- Focal neurological deficit. 4- Mentality changes. 5- Hydrocephalus. 6- Head lump ….. Features of increase intracranial pressure Focal neurological deficit  Clinical features Skull lump:  Classification of brain tumors Brain tumors are classified and graded by WHO according to presence of four morphological parameters which affect biological behavior. These histological features are: 1- Nuclear atypia. 2- Mitosis. 3- Vascular proliferation. 4- Necrosis.  Classification of brain tumors According to this we have 4 grades. grade I (benign) to grade IV malignant. Many of the grades have distinct name  e.g. Astrocytoma grade IV ➔ glioblastoma Multiform. astrocytoma grade III ➔anaplastic astrocytoma. Astrocytoma grade II ➔diffuse astrocytoma….. Classification according to cell of origin  Gliomas The most common group of primary brain tumors. 40-45% of brain tumors. The tumors are classified histologically on the resemblance of cells to glial cells. Major tumors includes: 1) Astrocytomas. 2) Oligodendrogliomas. 3) Ependymomas.  Astrocytoma Astrocytoma is a glioma that show astrocytes differentiation. Sub classification: Two major categories 1. Diffuse astrocytoma: diffuse infiltration of brain tissue. 2. Pilocytic astrocytomas.  Pilocytic astrocytoma Benign brain tumors with slow growth and good prognosis. WHO grade I. Usually arise in children and young adults. Usually located in the cerebellum, floor and walls of the third ventricle. Well circumscribed tumor with cystic areas.  Diffuse Astrocytomas Site: commonest site is cerebral hemispheres. Other sites include: cerebellum, brainstem, and spinal cord. Age: Usually fourth to sixth decades.  Classification of diffuse astrocytoma Diffuse astrocytomas can be further categorized according to their histologic differentiation and clinical course into: a. Well-differentiated astrocytoma (WHO grade II) b. Anaplastic astrocytoma (WHO grade III) c. Glioblastoma (WHO grade IV).  Well differentiated astrocytoma Morphology: Macroscopy: Poorly demarcated, infiltrative tumor. Microscopy Increased cellularity due to presence of astroglial tumor cells. Mild nuclear pleomorphism. Immunohistochemistry: reactive for GFAP (glial fibrillary acid protein)  Diffuse ill define tumor. Radiological findings morphology  Anaplastic astrocytomas Morphology: Poorly demarcated infiltrative tumor Microscopy: Increased cellularity Increase cellular and nuclear Pleomorphism. Anaplasia. Presence of mitotic figures.  Glioblastoma Gross: Consistency and color varies. ( # glioblastoma multiform ) Some areas are firm and white, others are soft and yellow due to necrosis or red due to hemorrhage. Show cystic degeneration.  Morphology: High grade brain tumor: necrosis, hemorrhage, infiltration….  Microscopy Similar to anaplastic astrocytoma with necrosis or vascular-endothelial cell proliferation.  Marked Increased cellularity Marked cellular and nuclear Pleomorphism Anaplasia Frequent mitoses. Necrosis. Vascular or endothelial cell proliferation& glomeruloid body formation. Microscopy of GBM  Types Primary glioblastoma: It arises de novo as new onset disease, without any pre-existing low grade astrocytoma and occurs at older age. Secondary glioblastoma: It arises in patient who had lower- grade astrocytoma earlier and occur in younger patients.  Treatment and prognosis Treatment: Surgery, chemotherapy and radiotherapy. Prognosis: Well-differentiated diffuse astrocytomas may remain static or progress slowly over years. Glioblastoma has a very poor prognosis (death usually occur in less than 1.5 years from time of diagnosis).  Embryonal Tumors Embryonal tumors are of neuroectodermal origin, which consists of primitive, undifferentiated cells ( small blue round cells). The most common is the medulloblastoma.  Medulloblastoma Highly malignant undifferentiated or embryonal tumor. Neuronal and glial markers may be expressed. Age: Occurs predominantly in children (majority at the end of the first decade). Constitutes about 20% of the brain tumors in children  Morphology Morphology Site: Exclusively occurs in the cerebellum. Children: In the midline of the cerebellum Adults: Lateral locations in the cerebellar hemispheres Gross/ Medulloblastoma  Microscopy: Highly cellular, composed of sheets of anaplastic (small blue) cells Numerous mitotic figures Homer-Wright (neuroblastic) rosette: It is characterized by central neutrophil (delicate pink material formed by neuronal processes) surrounded by primitive tumor cells may be seen. Immunohistochemistry: GFAP+. Microscopy  Spread Through the CSF, may present as nodular masses anywhere in the CNS. Metastases to the cauda equine  termed drop metastases.  Clinical Features Cerebellar dysfunction. Hydrocephalus due to occlusion of CSF flow caused by rapid growth of tumor.  Treatment and prognosis Surgery+ chemotherapy and irradiation. Prognosis: Poor for untreated patients. Good with total excision, chemotherapy, and irradiation. MYC amplification is associated with poor prognosis  Meningioma Occur in adults. Female > male. Arise from meningeal arachnoid cells. Associated with NF2 gene defect.  Classification Typical meningioma is benign ( WHO grade I). Atypical meningioma is WHO grade II. Anaplastic meningioma is WHO III. Morphology  Morphology Highly variable: Large polygonal cells, Psammoma bodies. May invade the bone.  Lymphoma CNS lymphomas occurs either as primary lymphomas or extra-CNS tumors, which have spread. Majority of primary CNS lymphomas are high grade diffuse B- cell lymphomas. Many systemic lymphomas may spread to the CNS, but Hodgkin lymphoma only very rarely does.  Primary CNS lymphomas Some of primary CNS lymphomas are associated with Epstein-Barr virus reactivation, particularly lymphomas occurring in immuno-compromised individuals. Often shows a periventricular distribution.  Metastatic brain tumors Represent about ¼ to ½ brain tumors. Lungs, kidneys, breast, malignant melanomas are the most common Primary. Metastatic pattern is different with different primary. Diffuse metastasis  Carcinomatous encephalitis. Thank you