Brain Tumors UMST

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

Which mutation is associated with the immortalization of tumor cells?

Mutations in microRNA genes

Mutations in tumor suppressor genes

Mutations in the promoter for telomerase (correct)

Mutations in the coding region of oncogenes

Which of the following genetic alterations is specifically noted in oligodendrogliomas?

CO-DELETION of 1p and 19q chromosomal segments (correct)

Translocation involving the BCR gene

Point mutations in the BRCA1 gene

Amplification of the MYC gene

What type of mutations are frequently associated with loss of cellular function in cancer?

Mutations that enhance telomerase activity

Mutations affecting DNA repair genes

Mutations in signaling pathways

P53 mutations (correct)

Which of the following factors contributes to tumor cell immortalization?

Increased expression of telomerase Signup and view all the answers

Which of the following mutations is not typically linked to tumor cell survival?

Chromosomal translocation of oncogenes Signup and view all the answers

Which type of brain tumor is specifically associated with a history of radiation exposure?

Meningioma Signup and view all the answers

What condition is linked to immunosuppression in HIV patients, particularly in relation to brain tumors?

Primary CNS lymphoma Signup and view all the answers

What is a common neurological feature produced by brain tumors?

Increased intracranial pressure Signup and view all the answers

Which of the following tumors is most likely to arise directly due to previous external beam radiation therapy?

Meningioma Signup and view all the answers

Radiation is considered a risk factor for which type of tumor?

Menigioma Signup and view all the answers

What role do inherited genetic mutations play in the context of brain tumors?

They contribute to the development of several autosomal dominant disorders. Signup and view all the answers

Which of the following disorders is NOT classified as an autosomal dominant condition associated with brain tumors?

Cystic fibrosis Signup and view all the answers

What effect does the overexpression of platelet-derived growth factors have in GII astrocytoma?

It leads to increased angiogenesis and tumor progression. Signup and view all the answers

Which statement accurately describes the relationship between GII astrocytoma and inherited conditions?

GII astrocytoma may be linked to genetic mutations in certain autosomal dominant disorders. Signup and view all the answers

Which of the following statements about the genetic basis of brain tumors is true?

Inherited genetic mutations significantly contribute to some types of brain tumors. Signup and view all the answers

What is the primary characteristic of anaplastic astrocytomas in terms of morphology?

Infiltrative tumor with poorly demarcated edges Signup and view all the answers

Which histological feature is NOT typically observed in anaplastic astrocytomas?

Presence of necrotic areas Signup and view all the answers

Which of the following terms best describes the cellular characteristics of anaplastic astrocytomas?

Pleomorphic with significant anaplasia Signup and view all the answers

What type of cellular change is particularly noted in the microscopic examination of anaplastic astrocytomas?

Increased nuclear pleomorphism Signup and view all the answers

Anaplastic astrocytomas are classified by which of the following microscopic features?

Presence of mitotic figures Signup and view all the answers

What characterizes primary glioblastoma in comparison to other types of glioblastoma?

It arises spontaneously as a new disease. Signup and view all the answers

At what age does primary glioblastoma typically occur?

At older age. Signup and view all the answers

Which statement about primary glioblastoma is false?

It is associated with low grade astrocytoma. Signup and view all the answers

What is a key distinction of primary glioblastoma compared to secondary glioblastomas?

Secondary glioblastomas arise from prior low grade tumors. Signup and view all the answers

Which of the following is NOT a characteristic feature of primary glioblastoma?

It is a result of genetic mutations. Signup and view all the answers

Which lymphoma is known to rarely spread to the central nervous system (CNS)?

Hodgkin lymphoma Signup and view all the answers

What virus is associated with reactivation in some primary CNS lymphomas?

Epstein-Barr Virus Signup and view all the answers

Which individuals are particularly associated with Epstein-Barr virus reactivation in primary CNS lymphomas?

Immuno-compromised individuals Signup and view all the answers

Which statement is true regarding systemic lymphomas and their spread to the CNS?

Hodgkin lymphoma rarely spreads to the CNS. Signup and view all the answers

What is a characteristic feature of primary CNS lymphomas?

Occasional association with Epstein-Barr virus Signup and view all the answers

Study Notes

Introduction

Brain tumors are a diverse group of neoplasms arising from various cell types within the brain, spinal cord, or meninges.
Tumors can be primary (originating from the CNS) or secondary (metastasis from other parts of the body).
The estimated incidence of brain tumors is 5-20 per 100,000 people.
All ages are affected, with distinct peaks in childhood (3-12 years) and adulthood (55-65 years).
CNS tumors account for about 20% of childhood cancers (second most common after leukemia).
Childhood CNS tumors differ from adult tumors in histological subtype and location (usually subtentorial in children versus supratentorial in adults).
Approximately 1¼-1½ of brain tumors are metastatic.
Tumors vary in behavior, from benign to highly malignant cancers.
They are a significant cause of morbidity and mortality due to their critical location, affecting vital neurological functions even if histologically benign.

Primary Brain Tumor

Originate from cells intrinsic to the CNS or its coverings.
Lack premalignant or in situ stages.
Even low-grade lesions are infiltrative, sometimes affecting large parts of the brain.
Patient course is influenced by growth patterns and location.
Rarely spread outside the CNS, infiltrating locally or reaching the subarachnoid space, potentially causing multiple implants in the brain or spinal cord.

Etiology and Pathogenesis

Genetic Factors:
- Mutations in isocitrate dehydrogenase (IDH) genes are linked to grade II astrocytomas and oligodendrogliomas. This leads to increased 2-hydroxyglutarate production, affecting enzymes regulating gene expression.
- Promoter mutations for telomerase contribute to tumor cell immortality.
- P53 mutations are also implicated.
- Chromosome 1p and 19q co-deletions are found in oligodendrogliomas.
- Overexpression of platelet-derived growth factors is associated with astrocytomas.
- Inherited genetic mutations are a major component of certain disorders, like neurofibromatosis, tuberous sclerosis, and von Hippel-Lindau syndrome.

Risk Factors

Radiation: Meningioma is an example.
Immunosuppression: Primary CNS lymphoma in HIV patients.

Pathology

Tumors produce neurological features by directly invading, infiltrating, and damaging brain tissue, disrupting function.
Intracranial tumor growth often accompanied by edema leads to increased intracranial pressure which may hinder/interrupt blood supply or cause herniation.
Tumors close to the ventricles can obstruct cerebrospinal fluid flow, resulting in hydrocephalus.

Diagnosis

Clinical Features: Patient age, gender, and neurological symptoms are assessed.
Radiological Diagnosis: Imaging Studies (X-rays, MRI, CT scans) are used to visualize the tumor.
Laboratory Diagnosis: Biopsy and genetic studies aid further characterization.

Clinical Features of Brain Tumors

Even small tumors can cause symptoms.
Symptoms of increased intracranial pressure include headache, vomiting, blurred vision, etc.
Convulsions, focal neurological deficits, mental changes, and hydrocephalus may occur.
A head lump can also be a symptom.

Features of Increased Intracranial Pressure

Headache (frontal, parietal, or occipital).
Nausea and/or vomiting.
Papilledema.

Focal Neurological Deficits

Bitemporal hemianopsia
Mental status changes
Speech and personality changes.
Motor weakness, seizures, or hypasthesias.
Balance difficulties

Skull lump.

Classification of Brain Tumors

Classified by WHO based on presence of four morphological parameters.
Parameters impact how the tumor progresses.
Histological Features:
- Nuclear atypia.
- Mitosis.
- Vascular proliferation.
- Necrosis.

Classification of Brain Tumors based on 4 Grades

Classified from grade I (benign) to grade IV (malignant).
Specific grade types carry distinct names.
- Astrocytoma grade IV = Glioblastoma Multiform.
- Astrocytoma grade III = Anaplastic astrocytoma.
- Astrocytoma grade II = Diffuse astrocytoma
- Additional classifications may exist based on cell or origin.

Gliomas

Most frequent group (40-45%) of primary tumors.
Classification is based on the glial cells they resemble.
- Astrocytomas.
- Oligodendrogliomas.
- Ependymomas.

Astrocytoma

Glioma that shows astrocytic differentiation.
Subclassifications:
- Diffuse astrocytoma: Diffuse infiltration of brain tissue.
- Pilocytic astrocytomas.

Pilocytic Astrocytoma

Benign, slow-growing tumor with good prognosis.
Typically occurs in children and young adults.
Commonly located in the cerebellum, floor, and walls of the third ventricle.

Diffuse Astrocytoma

Common site is cerebral hemispheres.
May also occur in cerebellum, brainstem, and spinal cord.
Typically occurs in fourth to sixth decades.

Well-differentiated Astrocytoma

Macroscopically: Poorly demarcated, infiltrative tumor.
Microscopically: Increased cellularity due to astroglial tumor cells, mild nuclear pleomorphism.
Immunohistochemistry: Positive for GFAP (glial fibrillary acidic protein).

Radiological Findings

Diffuse ill-defined tumor.

Anaplastic Astrocytomas

Poorly demarcated infiltrative tumor.
Increased cell numbers.
Increase cellular and nuclear pleomorphism.
Increased presence of mitotic figures (mitosis).

Glioblastoma

Gross: Variable consistency and color. May show firm white, soft yellow, and/or red areas, often caused by necrosis or hemorrhage.
Can show cystic degeneration.

High-Grade Brain Tumors

Morphology features: 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.

Primary Glioblastoma

Develops de novo without a previous low-grade astrocytoma.
Usually occurs in older adults.

Secondary Glioblastoma

Develops from a pre-existing lower-grade astrocytoma
Often occurs in younger patients

Treatment and Prognosis

Treatment strategies include surgical removal, chemotherapy, and radiation therapy.
Well-differentiated diffuse astrocytomas can remain stable or progress slowly over years.
Glioblastoma carries a poor prognosis, where death generally occurs within 1.5 years of diagnosis.

Embryonal Tumors

Originate from neuroectodermal cells, lacking differentiation (small blue round cells).
Medulloblastoma is a common example.

Medulloblastoma

Highly malignant embryonal/undifferentiated tumor.
Neuronal and glial markers may or may not be present.
Predominantly affects children (mostly at the end of the first decade of life).
Accounts for approximately 20% of childhood brain tumors.

Morphology (Medulloblastoma)

Exclusively in the cerebellum in children
Midline of cerebellum.
Lateral locations in adults
Microscopically: Highly cellular with sheets of anaplastic small blue cells, numerous mitotic figures.

Medulloblastoma Microscopy

Homer-Wright rosettes (central neutrophils surrounded by primitive tumor cells) are characteristic.
Immunohistochemistry: Positive for GFAP (glial fibrillary acidic protein).

Spread

CSF dissemination, may present as nodular masses throughout CNS.
Drop metastases to the cauda equina.

Clinical Features (Medulloblastoma)

Cerebellar dysfunction or issues.
Hydrocephalus due to CSF flow occlusion caused by rapid tumor growth.

Treatment and Prognosis (Medulloblastoma)

Treatment includes surgery, chemotherapy, and irradiation.
Poor outcome for untreated patients.
Good outcome with extensive excision, chemotherapy, and radiation therapy.
MYC amplification is associated with poor prognosis.

Meningioma

Occur in adults (females more than males).
Arises from meningeal arachnoid cells.
Associated with an NF2 gene defect.
Classifications:
- Typical meningioma (WHO grade I) - benign
- Atypical meningioma (WHO grade II)
- Anaplastic meningioma (WHO grade III)

Morphology (Meningioma)

Highly variable, with large polygonal cells, psamomma bodies, and potential bone invasion.

Lymphoma

May occur as primary CNS lymphomas or from extra-CNS spread.
Primarily high-grade diffuse B-cell lymphomas.
Several systemic lymphomas can potentially spread to the CNS, but Hodgkin lymphoma exceptionally rarely does.

Primary CNS Lymphomas

Some associated with Epstein-Barr virus reactivation, especially in immunocompromised individuals.
Often exhibit a periventricular distribution.

Metastatic Brain Tumors

Constitute about 25% of all brain tumors.
Often originate from lung, kidney, breast, or malignant melanoma, most commonly
Varying metastatic patterns linked to specific tumor types.
Diffuse metastases can manifest as carcinomatous encephalitis.

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Description

Test your knowledge on the various genetic mutations associated with brain tumors and their implications in tumor cell immortalization. This quiz covers factors contributing to tumor types, risks associated with radiation, and related neurological features. Perfect for those studying oncology or neurobiology!