Neuro_Oncology_Flashcards

Question 1

Topic

Answer 1

Details

Question 2

Introduction

Answer 2

Speaker: Prof. Steve Gentleman
Focus: Tumors in the central and peripheral nervous systems, interaction with neurosurgeons, diagnosis, and treatment.
Context: Part of a broader lecture series covering neuropathology, including cerebrovascular issues, trauma, and neurodegenerative diseases.

Question 3

Overview of CNS and PNS Tumors

Answer 3

Central Nervous System (CNS): Includes the brain, meninges, spinal cord, and pituitary gland.
Peripheral Nervous System (PNS): Includes nerves in various organs, cranial nerves, spinal nerves, and Schwann cells (myelinating cells in the periphery).

Question 4

Classification

Answer 4

Primary Tumors: Originate within the CNS (rare in adults, more common in children).
Secondary Tumors: Metastases from systemic cancers (10 times more frequent than primary CNS tumors).

Question 5

Classification by Location

Answer 5

Extra-axial: Tumors in the coverings (e.g., meninges), cranial bones, soft tissues, and nerves.
Intra-axial: Tumors within the brain parenchyma, derived from glial cells, neurons, neuroendocrine cells, lymphomas, and germ cell tumors.

Question 6

Primary CNS Tumors (WHO Grades)

Answer 6

Grade 1: Non-malignant (e.g., pituitary adenomas, meningiomas).
Grade 2-4: Malignant (e.g., gliomas, with glioblastoma being the most severe, Grade 4).

Question 7

Risk Factors for CNS Tumors

Answer 7

Unknown Etiology: Majority of primary CNS tumors have no known cause.
Environmental Factors: Previous radiotherapy in the head and neck increases the risk of meningiomas and gliomas.
Genetic Predisposition: Less than 5% of primary brain tumors are familial, with syndromes like Neurofibromatosis (types 1 and 2), Li-Fraumeni syndrome, Turcot syndrome, and von Hippel-Lindau disease.

Question 8

Clinical Presentation

Answer 8

Symptoms: Persistent headaches, intracranial hypertension (headaches, vomiting, mental status changes), focal neurological deficits, seizures, personality changes, motor signs (cerebellar ataxia, long tract signs), cranial nerve palsies.
Tumor Location:
- Supratentorial (above the tentorium): Symptoms vary based on the tumor’s location within the brain.
- Infratentorial (below the tentorium): More likely to present with motor signs, cerebellar ataxia, and cranial nerve deficits.

Question 9

Diagnosis

Answer 9

Imaging:
- CT Scan: Basic imaging modality.
- MRI: Provides more detailed images of parenchymal tumors.
- MRI Spectroscopy: Assesses metabolic activity.
- Perfusion MRI and Functional MRI: Evaluate blood flow and brain function.
- PET Scan: Research tool for assessing tumor metabolism and distribution.
Biopsy: Necessary for definitive diagnosis and determining tumor type and grade.

Question 10

Treatment Approaches

Answer 10

Surgery:
- Goals: Maximal safe resection with minimal damage to adjacent normal tissue.
- Techniques: Craniotomy for debulking, open biopsies for diagnosis, and stereotactic biopsies for inaccessible tumors.
- Intraoperative Tools: Mass spectrometry for real-time tissue analysis.
Radiotherapy: Used for low and high-grade tumors, metastases, and some benign tumors.
Chemotherapy: Primarily for high-grade gliomas (e.g., temozolomide), with mixed outcomes. Other agents include EGFR inhibitors and PD-L1 inhibitors.

Question 11

Histopathology and Molecular Pathology

Answer 11

Histopathological Classification:
- Based on the tumor’s cellular origin (e.g., astrocytomas from astrocytes, oligodendrogliomas from oligodendrocytes).
- Tumor behavior predicted by histological type.
Grading System:
- Grade 1: Benign with long-term survival (e.g., meningiomas).
- Grade 2-3: Intermediate malignancy with variable survival rates.
- Grade 4: Highly malignant with poor prognosis (e.g., glioblastomas).
Molecular Markers: Increasingly important for diagnosis and prognosis. Common markers include IDH mutations, EGFR, and PTEN mutations.

Question 12

Examples of CNS Tumors

Answer 12

Diffuse Gliomas:
- Grades 2-4: Includes astrocytomas and oligodendrogliomas, with potential for malignant progression.
- IDH Mutations: Associated with better prognosis and response to therapy.
Circumscribed Gliomas:
- Pilocytic Astrocytoma (Grade 1): Common in children, good prognosis, often in the posterior fossa.
- Histology: Characteristic ‘hairy’ cells (Rosenthal fibers), low mitotic activity.
Glioblastoma Multiforme (GBM):
- Grade 4: Most frequent and aggressive, median survival of 8 months, highly infiltrative and vascular.
- Histology: Heterogeneous with areas of necrosis and angiogenesis.

Question 13

Meningiomas

Answer 13

Grades 1-3: Extra-axial, usually benign but can recur. Associated with neurofibromatosis type 2.
Histology: Mitotic activity determines grade, with higher grades showing brain invasion.

Question 14

Metastases

Answer 14

Most common CNS tumors, often multiple and poor prognosis. Common primaries include lung, breast, melanoma, and renal cell carcinoma.

Question 15

Medulloblastoma (WHO Grade 4)

Answer 15

Description: Embryonal tumor in the cerebellum, rare but most common brain malignancy in children.
Diagnosis: MRI shows large posterior fossa tumors, resected specimen shows a midline or lateral mass.
Histological and Molecular Subtypes: Multiple subtypes with varying prognosis, improved outcomes with chemotherapy and radiotherapy.

Question 16

Emerging Techniques and Future Directions

Answer 16

Methylation Profiling: Characteristic patterns of DNA methylation provide insights into tumor type and origin.
Molecular Classification: Moving towards a more molecular-based classification, steering treatment strategies and prognosis.

Question 17

Pathology Specifics

Answer 17

WHO Grading System:
- Grade 1: Low proliferative potential, often curable with surgery alone (e.g., meningiomas).
- Grade 2: Increased mitotic activity, risk of recurrence (e.g., atypical meningiomas).
- Grade 3: Malignant, requires aggressive treatment, high recurrence (e.g., anaplastic astrocytomas).
- Grade 4: High-grade malignancies, rapid progression, poor prognosis (e.g., glioblastomas).
Histological Markers:
- Mitotic Figures: Indicators of cell proliferation.
- Necrosis: Areas of cell death within tumors.
- Microvascular Proliferation: Indicates aggressive tumor behavior.

Question 18

Molecular Markers

Answer 18

IDH1/IDH2 Mutations: Found in lower-grade gliomas and secondary glioblastomas, associated with better prognosis.
1p/19q Co-deletion: Characteristic of oligodendrogliomas, associated with better response to therapy.
EGFR Amplification: Common in primary glioblastomas, associated with poor prognosis.
MGMT Promoter Methylation: Predicts response to alkylating agents like temozolomide.

Question 19

Peripheral Nervous System Tumors

Answer 19

Schwannomas: Benign tumors arising from Schwann cells, often associated with neurofibromatosis type 2.
Neurofibromas: Benign tumors from peripheral nerves, associated with neurofibromatosis type 1.
Malignant Peripheral Nerve Sheath Tumors (MPNST): Rare, aggressive tumors, can arise from pre-existing neurofibromas.

Question 20

Summary

Answer 20

Neuro-oncology: Involves the diagnosis and treatment of CNS and PNS tumors, with a multidisciplinary approach.
Key Aspects: Clinical presentation, imaging, histopathology, molecular markers, and treatment strategies.
Challenges and Future Directions: Improving diagnostic accuracy, developing targeted therapies, and understanding the molecular basis of tumors for better management.