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Flashcards in Modern Neuropathology Deck (22)
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1

Definition of tumor:

swelling formed by an abnormal growth of cells

2

Benign vs malignant tumors

Benign:
- may be live threatening
- almost never grown back
- have an obvious edge or border
- may become malignant
Malignant:
- always live threatening
- likely to grow back
- may spread to other parts of the body

3

Brain-related tissues which may grow tumors:

- bone
- meninges
- blood vessels
- astrocytes
- neurons

4

Most pervasive tumors:

- breast for females
- prostate for males
- lung
- bowel

5

How prevalent are tumors of the brain and nervous system?

Invasive tumors of the brain and central
nervous system (CNS) rank 13th"highest
in males and 17th highest in females;
however, when the non-invasive brain
and CNS tumors are also included in the
total, the ranks are 11th and 8th highest,
respectively (data not shown)

6

Mechanisms by which intracranial tumors produce symptoms:

- compression of axons
- destruction of axons
- increasing intracranial pressure (Monro-Kellie doctrine)
- oedema
- hydrocephalus

7

General symptoms of intracranial tumors

- headaches (worse in the morning)
- nausea & vomiting
- problems balancing & walking
- changes in mood, personality, concentration
- problems with memory

8

Focal symptoms of intracranial tumors

- changes in speech, vision, hearing (depending on location)
- muscle jerking, twitching,
- numbness or tingling in arms or legs
- muscle weakness/paralysis

9

Approaches to diagnosing intracranial tumors

- neurological examination
- imaging (CT/MRI)
- spinal tap
- biopsy

10

Types of radiation therapy and its side effects:

❖ Classical radiation: Photon
❖ Stereotactic radiation: Gamma-knife
❖ Particle therapy: Proton/Carbon-ion

Side effects:
❖ Oedema
❖ (Radio)necrosis
❖ Radiation-induced meningioma or schwannoma

11

Most common brain tumors:

1. Meningioma
2. Astrocytoma
3. Vestibular schwannoma
4. Pituitary adenoma

12

Meningioma details

❖ Account for 14-20% of all intracranial neoplasms!
❖ Arise from the arachnoid mater (not dura)!
❖ Women to men ratio of 2:1!
❖ More common in patients > 40 years!
❖ Grade I in 88-95% of cases, rarely grade II or III!
❖ Grows slowly!
❖ Surgery when documented growth on serial imaging and/or symptoms
referable to the lesion

13

Astrocytoma details

❖ 50% of all intracranial tumors!
❖ Derived from astrocytes: Supporting glial cells!
❖ Grade I to IV

Low-grade:
❖ 10 - 15% of astrocytoma!
❖ Epidemiology: Biphasic distribution!
❖ Childhood (6-12y)!
❖ Early adulthood (26-46y)!
❖ Histology benign, but may become malignant!
❖ Rarely cured because they cannot be completely excised

High-grade:
❖ Grade IV: Glioblastoma multiforme (GBM)!
❖ 15-25% of all intracranial tumors!
❖ Rapid growth!
❖ Worst prognosis of all CNS tumors!
❖ Median survival:!
❖ Without treatment: 3 months!
❖ With treatment: 1-2 years!
❖ Therapy: Surgery, Radiotherapy and chemotherapy

14

Vestibular Schwannoma details

❖ = Acousticus neurinoma!
❖ 5-10% of all intracranial tumors!
❖ Histological benign!
❖ Common early symptom triad:!
❖ Hearing loss!
❖ Tinnitus!
❖ Dysequilibrium!
Management:!
❖ Follow symptoms, hearing and tumor growth on serial MRI!
❖ Radiation therapy!
❖ Surgery

15

Pituitary adenoma details

❖ 15-20% of all intracranial tumors!
❖ Benign!
❖ Symptoms: !
❖ Hormone oversecretion/underproduction!
❖ Mass effect: !
❖ Compression optic chiasm!
❖ Obstructive hydrocephalus!
Treatment:!
❖ Surgery!
❖ Hormone substitution

16

Types of cancer treatments currently being researched:

❖ Cell lines!
❖ Xenograft model!
❖ GEM model

17

Gene expression analysis methods used in cancer research:

mRNA:!
❖ Quantitative reverse transcriptase PCR!
❖ Next generation sequencing!
❖ Genechip microarray!
protein:!
❖ Westernblot!
❖ Immunohistochemistry!
❖ Mass spectrometer

18

Viruses in cancer:

❖ Viruses cause cancer by interfering with cell-cycle controls
❖ Papillomavirus binds to the protein products of two key tumor suppressor genes, Rb and p53, putting them out of action

❖ Elimination of these proteins allows the abnormal cell to survive, divide and accumulate more abnormalities

There are many oncoviruses known:
❖ Human papillomavirus
❖ Epstein-Bar virus
❖ Merkel cell polyomavirus

19

Three common models for pre-clinical testing of cancer therapeutic agents

❖ Cell lines!
❖ Xenograft model!
❖ GEM model

20

Using cell lines - pros & cons

❖ Tumor cells can be brought into culture!
❖ Represents the original tumor!
❖ Can be used to test therapeutic agents!

Advantages:
❖ Relatively cheap !
❖ Many different conditions can be tested in small well plates!
❖ Cells can be frozen en thawed for later use!
Disadvantages:
❖ Genotypic and phenotypic drift!
❖ No histology

21

Xenograft details:

❖ Tumor cells injected subcutaneously in athymic, nude mice!
❖ Testing of therapeutic agents!
❖ Disadvantage:!
❖ Testing of drug response does often not correlate with clinical activity in patients

22

The chance of a brain tumor being malignant:

ca. 50%