Cancer Biology: Tumor Genetics and Brain Tumors

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Questions and Answers

Which genetic alteration is specifically associated with the immortalization of tumor cells?

Co-deletion of 1p and 19q

Chromosomal translocations

Mutations in the promoter for telomerase (correct)

P53 mutations

What chromosomal segments are co-deleted in oligodendrogliomas?

1p and 19q (correct)

1p and 20q

1q and 19p

1p and 18q

Which of the following is a consequence of P53 mutations in cancer?

Increased telomerase activity

Altered apoptosis regulation (correct)

Enhanced angiogenesis

Promoter activation of oncogenes

Which mechanism is involved in tumor cell immortality?

Mutations in the telomerase promoter Signup and view all the answers

What is the result of co-deletion of 1p and 19q in certain brain tumors?

Identification of oligodendrogliomas Signup and view all the answers

Which type of brain tumor is primarily associated with nerve sheath cells?

Schwanomas Signup and view all the answers

What type of cells are meningiomas derived from?

Arachnoid cells Signup and view all the answers

Which of the following is categorized as a primitive neuroectodermal tumor?

Neuroblastomas Signup and view all the answers

Which group of tumors represents the most common type of primary brain tumor?

Gliomas Signup and view all the answers

Which of the following tumors primarily derives from lympho-reticular cells?

Lymphomas Signup and view all the answers

Which type of lymphoma is noted for rarely spreading to the CNS?

Hodgkin lymphoma Signup and view all the answers

What is a potential cause of some primary CNS lymphomas in immuno-compromised individuals?

Epstein-Barr virus reactivation Signup and view all the answers

Which of the following lymphomas is predominantly associated with the central nervous system?

Primary CNS lymphoma Signup and view all the answers

In which context is Hodgkin lymphoma more likely to occur in the CNS?

Among immunocompromised individuals Signup and view all the answers

What common feature is shared by many systemic lymphomas regarding their spread?

They can metastasize to the CNS. Signup and view all the answers

What factor contributes to the significant morbidity and mortality associated with CNS tumors?

Their location affecting vital neurological functions Signup and view all the answers

Which characteristic defines primary brain tumors?

They arise from cells intrinsic to the CNS or its coverings Signup and view all the answers

How do CNS tumors vary in behavior?

They range from benign growths to highly malignant cancers Signup and view all the answers

What is a common misconception about benign CNS tumors?

They do not pose any health risks Signup and view all the answers

Why are CNS tumors particularly concerning despite being benign?

They can cause severe neurological impairments Signup and view all the answers

What is the approximate proportion of brain tumors that are classified as metastatic?

¼ to ½ Signup and view all the answers

Which of the following primary cancers is NOT commonly associated with metastatic brain tumors?

Prostate cancer Signup and view all the answers

How does the metastatic pattern of brain tumors change?

It varies depending on the type of primary cancer. Signup and view all the answers

Which distribution pattern is often associated with metastatic brain tumors?

Periventricular distribution Signup and view all the answers

What is the most common origin of metastatic brain tumors?

Kidney Signup and view all the answers

What does GFAP+ indicate in immunohistochemistry analysis?

Presence of glial fibrillary acidic protein Signup and view all the answers

What might nodular masses in the CNS typically indicate?

Metastatic cancer spread Signup and view all the answers

What are drop metastases specifically associated with?

Metastases to the cauda equina Signup and view all the answers

Which clinical feature is commonly observed in patients with advanced CNS metastases?

Cerebellar dysfunction Signup and view all the answers

How does cancer spread through the CNS?

Through the cerebrospinal fluid Signup and view all the answers

Study Notes

Introduction to Brain Tumors

Brain tumors are diverse neoplasms originating from various cell types—brain, spinal cord, or meninges.
They can be primary (originating in the CNS) or secondary (metastatic from other cancers).

Epidemiology of Brain Tumors

Estimated incidence of brain tumors is 5-20 per 100,000 people.
All ages are affected, with peaks in childhood (3-12 years) and adulthood (55-65 years).
Brain tumors account for about 20% of childhood cancers (second most common after leukemia).
Childhood tumors are usually located in the sub-tentorial area, while adult tumors are often supra-tentorial.
Approximately 25-50% of brain tumors are metastatic.

Types of Brain Tumors

CNS tumors have variable behaviors, from benign to highly malignant cancers.
They cause significant morbidity and mortality due to their location. Benign tumors can still impact vital neurological functions.
Primary brain tumors arise from cells intrinsic to the CNS or its coverings. They do not exhibit pre-malignant or in situ stages.
Low-grade tumors are infiltrative, often affecting widespread areas of the brain.
Tumor growth and anatomical location directly impact patient course.
Tumors rarely spread beyond the CNS—tumors invade locally or reach the subarachnoid space, creating multiple implants in the brain or spinal cord.

Etiology and Pathogenesis

Genetic Factors:
- Mutations in Isocitrate Dehydrogenase (IDH) genes are common in grade II astrocytomas and oligodendrogliomas. These mutations increase 2-hydroxyglutarate production. This interferes with enzymes regulating gene expression.
- Mutations in the telomerase promoter contribute to tumor cell immortality.
- P53 mutations are also involved.
Inherited Genetic Mutations:
- Co-deletion of 1p and 19q chromosomal segments is common in oligodendrogliomas.
- Overexpression of platelet-derived growth factors is observed in certain astrocytomas.
- Inherited genetic mutations are a component of some autosomal dominant disorders, such as neurofibromatosis, tuberous sclerosis, and von Hippel-Lindau syndrome.

Risk Factors

Radiation: Meningiomas are an example of radiation-related brain tumors.
Immunosuppression: Primary CNS lymphoma is associated with immunosuppression, particularly in HIV/AIDS patients.

Pathology of Brain Tumors

Neurologic Features: Brain tumors produce neurological effects by:
- Directly invading, infiltrating, and damaging brain tissue, impacting functions.
- Causing edema+ new blood vessels, and raising intracranial pressure, thereby affecting blood supply and leading to herniation.
- Obstructing cerebrospinal fluid flow, leading to hydrocephalus.

Diagnosis of Brain Tumors

Clinical Features: Patient age, gender, and neurological features are crucial diagnostic components.
Radiological Diagnosis: Imaging studies like X-rays, MRI, and CT scans are essential diagnostic tools.
Laboratory Diagnosis: Biopsies and genetic studies help confirm diagnoses and assess tumor characteristics.

Clinical Features of Brain Tumors

Intracranial Pressure Symptoms: Headache, vomiting, blurry vision.
Neurological Deficits: Focal neurological deficits and cognitive changes may occur.
Seizures: Seizures are a common symptom.
Mass Effects: A head lump may be present.

Classification of Brain Tumors

WHO Classification: Brain tumors are classified based on morphological features (nuclear atypia, mitosis, vascular proliferation, and necrosis) affecting biological behavior.
Grades: Tumor grading ranges from grade I (benign) to grade IV (malignant). Different tumor types are assigned distinct names (e.g. glioblastoma multiforme).
Cellular Origin: Tumors are also categorized according their cell of origin e.g glioma.

Gliomas

Most common primary brain tumors (40-45%).
Histologically classified based on their resemblance to glial cells

Astrocytomas

Astrocytoma is a glioma type, showing astrocyte differentiation.
- Subtypes
  - Diffuse Astrocytomas: Infiltrative tumors affecting brain tissue, characterized by diffuse infiltration.
  - Pilocytic Astrocytomas: Benign brain tumors with a good prognosis, commonly occurring in children and young adults; frequently located in the cerebellum, floor, and walls of the third ventricle.

Anaplastic Astrocytomas

Usually exhibits poorly demarcated infiltrative morphology
Characterized by increased cellularity, increase cellular and nuclear pleomorphism and anaplasia
Also characterized by frequent mitoses.

Glioblastoma

Gross features: Tumor consistency and color can vary. Areas may include firm white tissue, soft yellow necrotic areas, or red hemorrhagic regions. Cystic degeneration is also observed.
Morphology: High-grade brain tumors often show necrosis, hemorrhage, and infiltration..
Microscopic features: Similar to anaplastic astrocytoma but also exhibits necrosis, marked increased cellularity, marked cellular and nuclear pleomorphism, anaplasia, and frequent mitoses. Vascular or endothelial cell proliferation with glomeruloid body formation may also be observed.

Embryonal Tumors (Medulloblastoma)

Characteristics: Highly malignant, undifferentiated, neuroectodermal tumors composed of primitive, undifferentiated cells (small blue round cells).
Most common type is medulloblastoma. Neuronal and glial markers may be expressed.
Age of onset: Commonly diagnosed in children (mostly at the end of the first decade).
Location: Exclusively in the cerebellum (midline in children, lateral in adults).

Spread of Brain Tumors

CSF spread: Can present as nodular masses throughout the CNS.
Drop metastases: Metastasis to the cauda equina called "drop metastases.”

Clinical features of brain tumors

Cerebellar Dysfunction: Issues with coordination and balance.
Hydrocephalus: CSF flow obstruction causing fluid buildup in the brain.

Treatment

Treatment Options: Surgery, chemotherapy, and radiotherapy are implemented to manage brain tumors.

Prognosis

Well-differentiated diffuse astrocytomas: Slow growth, static progression, or slow development over several years.
Glioblastoma: Extremely poor prognosis; patients often die within 1.5 years of diagnosis.
Other tumors: Vary based on tumor type.

Meningiomas

Occur in adults, with females more frequently affected than males.
Originate from meningeal arachnoid cells.
Associated with NF2 gene defects.
Types
- Benign (WHO grade I).
- Atypical (WHO grade II).
- Anaplastic (WHO grade III).
Morphology: Highly variable; large polygonal cells, psammoma bodies; may invade bone.

Lymphomas

CNS lymphomas may occur as primary or metastatic lesions.
Diffuse large B-cell lymphomas are the dominant subtype of primary CNS lymphoma.
Many systemic lymphomas spread to the CNS, but Hodgkin's lymphoma is rare.
Some CNS lymphomas are associated with Epstein-Barr virus reactivation. Distribution is often seen in periventricular areas.

Metastatic Brain Tumors

Tumors originate from other areas in primary parts of the body (lungs, kidneys, breast, malignant melanomas).
Diffuse metastasis and carcinomatous encephalitis are typical patterns.

General note

The information provided is for educational purposes and should not be used for self-diagnosis or treatment. Consult a medical professional for accurate diagnoses and care.

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Description

Test your knowledge on the genetics of cancer and brain tumors with this quiz. Explore topics such as P53 mutations, chromosomal deletions in oligodendrogliomas, and the characteristics of various brain tumors. This quiz covers essential concepts in tumor biology and pathology.