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Neuro Flashcards

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1
Q

GLIOMAS

A

GLIOMAS

  • Astrocytoma
  • Oligodendroglioma
  • Ependymoma
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2
Q

Astrocytomas

  • Infiltrating
  • Non-infiltrating
A

Astrocytomas

  • Infiltrating
    • Diffuse astrocytoma
    • Anaplastic astrocytoma
    • Glioblastoma
    • Gliomatosis cerebri
  • Non-infiltrating
    • Pilocytic astrocytoma
    • Pleomorphic xanthosastrocytoma
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3
Q

Infiltrating Astrocytoma

  • __% of primary adult tumors
  • Location
  • Spectrum of histologic grades:
    • WHO Grade II:
    • WHO Grade III:
    • WHO Grade IV:
  • Age:
    • Diffuse astrocytoma:
    • Anaplastic astrocytoma:
    • GBM:
  • High grade (III and IV): __ therapy
A

Infiltrating Astrocytoma

  • 80% of primary adult tumors
  • Cerebral hemispheres most common
  • Spectrum of histologic grades:
    • WHO Grade II: diffuse astrocytoma
    • WHO Grade III: anaplastic astrocytoma
    • WHO Grade IV: glioblastoma
  • Age:
    • Diffuse astrocytoma: 35 y/o
    • Anaplastic astrocytoma: 45 y/o
    • GBM: 60 y/o
  • High grade (III and IV): adjuvant therapy
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4
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A
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5
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6
Q
A

Glioblastoma, WHO grade IV

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7
Q

Astrocytic Genetics

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Astrocytic Genetics

  • Low Grade: p53 mutations and over expression of PDGF-A and its receptors
  • Isocitrate dehydrogenase I (IDH 1), a metabolic enzyme in the citric acid cycle, is commonly mutated in astrocytomas, oligodendroglioma, and mixed gliomas- low grade (II) and anaplastic (III). Associated with better prognosis.
  • Primary Glioblastomas: MDM2 amplification, mutated/ aberrant expression of EGFR/p16 deletion/ PTEN mutation
  • Better response to chemotherapy: Methylation of promoter for gene encoding MGMT.
  • 10q/PTEN deletion (e.g., whole-arm loss): predominantly astrocytic ‘signature’; comprises independent negative prognostic factor
  • EGFR amplification (chromosome 7): evident in ‘primary’ glioblastomas (small-cell cytophenotype); comprises independent negative prognostic factor
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8
Q
A

Gemistocytic astrocytoma

  • p53 positive
  • Prone to progress to anaplastic and GBM
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9
Q

Non-infiltrating Astrocytomas

  • Pilocytic astrocytoma
    • Grade
    • Age
    • Location
    • Genetics
  • Pleomorphic xanthosastrocytoma
    • Grade
    • Age
    • Location
A

Non-infiltrating Astrocytomas

  • Pilocytic astrocytoma
    • Grade I
    • Children and young adult
    • Cerebellum, thalamus, optic nerve
    • NF1
  • Pleomorphic xanthosastrocytoma
    • Grade II
    • Children and young adults
    • Temporal lobe most common
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10
Q
A

Pilocytic astrocytomas, WHO Grade I

  • Biphasic appearance (compact or loose)
  • Compact area: Rosenthal fibers
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11
Q
  • Age
  • Location
  • Interval to anaplastic progression
  • __ deletion, oligodendroglial ‘signature’; connotes chemosensitivity
A

Oligodendroglioma

  • 5-15% of gliomas
  • Age: 40 ~ 50 y/o, rare in children
  • Restricted to supratentorial compartment
  • Interval to anaplastic progression is longer relative to astrocytoma (range 9y, vs 4-5y for latter)
  • 1p, 19q deletion, oligodendroglial ‘signature’; connotes chemosensitivity
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12
Q
A

Ependymoma

  • Incidence: 5% to 10% of primary brain tumors in the 1st two decades
  • Arise around ventricular lining
  • Locations:
    • The 4th ventrical: common in children
    • Spinal: adults, mean 40 yrs, NF2
  • Loss/mutation of NF2 on chromosome 22q in spinal cord tumors
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13
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A
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14
Q

Neuronal/Glioneuronal Tumors

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Neuronal/Glioneuronal Tumors

  • Ganglioglioma
  • Dysembryoplastic Neuroepithelial tumor (DNT)
  • Central Neurocytoma
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15
Q
A

Ganglioglioma, GI

  • Bi-nucleate, dysmorphic neurons
  • Low grade astrocytomas
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16
Q

Poorly Differentiated/ Embryonal Tumors

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Poorly Differentiated/ Embryonal Tumors

  • Malignant small blue cell tumors
  • Grade IV
  • Young Children
  • Based on location:

– Medulloblastoma

– Primitive Neuroectodermal tumor of the Central Nervous System (PNET)

– Atypical Teratoid/ Rhabdoid Tumor (ATRT)

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17
Q
A

Medulloblastoma

  • 20% of pediatric brain tumors
  • Posterior fossa
  • Spreads by CSF seeding along the subarachnoid space
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18
Q
A

Primitive Neuroectodermal Tumor

  • Supratentorial tumors
  • Histologically identical to medulloblastomas, genetically differ from medulloblastomas and peripheral PNET (lack Ewing’s translocations)
  • Homer-Wright rosette
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19
Q
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20
Q
A

Atypical Teratoid/Rhabdoid tumor

  • 2% of pediatric brain tumors
  • Highly malignant of young children/infants (up to 5 years of age)
  • “Rhabdoid” cells
  • Multiple lineage markers (epithelial , muscle)
  • Molecular Genetics: >90% of cases show loss/mutations of hSN5/INI1 gene on chromosome 22
  • IHC: loss of normal nuclear staining for INI1
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21
Q
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A

Meningioma

  • Benign tumors of adults
  • Locations:
    • Attached to dura, arise from arachnoid meningothelial cells
    • Intraventricular, arise from stromal arachnoid cells of choroid plexus
  • Slight female predominance (3:2)
  • Often express progesterone receptors
    • Rapid growth during pregnancy
  • Cytogenetics
    • loss of chromosome 22q
    • Multiple meningiomas associated with NF2
22
Q

Meningioma Grades and subtypes

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A

Meningioma Grades and subtypes

  • Grade I (92%): most common, “cure” possible with complete resection
    • Meningothelial, fibrous, transitional, psammomatous, angiomatous, microcystic, secretory, lymphoplasmacyte-rich, mataplastic
  • Grade II (7%): higher rate of recurrence
    • Atypical, clear cell, chordoid
  • Grade III (rare): highly aggressive
    • Anaplastic, rhabdoid, papillary
23
Q
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A

Anaplastic Meningioma

24
Q
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A

Clear Cell Meningioma

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Atypical Meningioma
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Psammomatous Meningioma
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Fibrous Meningioma
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Pituitary Adenoma
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Subepencymoma, WHO Grade I * 4 th & lateral ventricles, cervical cord * Low-power microscopic appearance is diagnostic
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Neurofibroma, WHO Grade I * Locations: skin, peripheral nerves, spinal nerve roots * Most neurofibromas in spinal nerve roots are associated with NF1
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Adamantinomatous craniopharyngioma, WHO Grade I * Suprasellar, usually with intrasellar extension. * Surgically curable
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Papillary craniopharyngioma, WHO Grade I * Exclusively in adults, at a mean age of 40-55 years * Well-differentiated squamous epithelium without keratin, less palisading
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Hemangioblastoma, WHO Grade I * Cerebellum, brain stem, spinal cord * usually an enhancing nodule within a cyst * Associated (25%) with von Hippel-Lindau disease
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Chordoma * locations: clivus, sacrum, cervical spine * Lobules and chords of cells in a mucoid matrix * Locally aggressive * Median survival: 6 years * Keratin + * Brachyury +
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Pleomorphic Xanthoastrocytoma (PXA), WHO GRADE II * Discrete, superficial cerebral, +/- cystic, often involves meninges * Preferentially children & young adults; 10-year survival: 70% * Highly atypical, bizarre astrocytes – don’t confuse with glioblastoma!
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Paraganglioma, WHO Grade I * Locations: cauda equina, jugulotympanic, carotid body * Chief cells: chromogranin+, synaptophysin+; sustentacular cells: S-100+
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Hemangiopericytoma, WHO Grade II or III * High risk of local recurrence and metastasis * EMA negative (unlike meningioma)
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Germinoma * Most common CNS germ cell tumor * Children and young adults * Usually in the pineal or suprasellar region
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Central Neurocytoma, WHO Grade II * Typically arises in the region of foramen of Monro * Resembles an oligodendroglioma but is noninfiltrative and synaptophysin+ * Benign, but total resection is not always possible * 5-year survival:80%
40
Metastatic Tumor to Brain
Metastatic Tumor to Brain * 15% of surgically treated brain tumors are metastases * Mets have a noninfiltrative border and are CAM5.2+, primary tumors are CAM 5.2-(don’t use AE1/AE3) * Most common primaries: * Lung 18-60 % * Breast 5-21% * Melanoma 16% * Colon cancer 5-12% * Renal cell carcinoma 3-10%
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Foamy macrophages suggest an inflammatory or nonneoplastic process * Multiple sclerosis * Subacute infarct * Progressive multifocal leukoencephalopathy (PML)
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Familial Tumor Syndromes Involving the nervous System
Familial Tumor Syndromes Involving the nervous System * Neurofibromatosis type I * Neurofibromatosis type 2 * Li-Fraumeni Syndrome * Turcot Syndrome * Gorlin Syndrome (Naevoid Basal Cell Carcinoma Syndrome) * Von Hippel-Lindau * Tuberous Sclerosis * Cowden Syndrome
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* Gene: * Chromosome: * Neurvous system: * Skin: * Others:
Neurofibromatosis type I * Gene: NF1 * Chromosome: 17q11 * Neurvous system: * Neurofibroma * MPNST * optic nerve glioma * astrocytoma * PSAMMOMATOUS CARCINOID • Almost exclusively seen in the ampullary/periampullary location * Skin: * Café-au-lait spots * axillary freckling * Others: * iris hamartomas * osseous lesions * phaeochromocytoma * leukaemia
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* Gene: * Chromosome: * Neurvous system: * Others:
Neurofibromatosis type 2 * Gene: NF2 * Chromosome: 22q12 * Nervous system: * schwannoma * meningiomas * meningioangiomatosis * spinal ependymoma * astrocytoma * Others: * posterior lens opacities * retinal hamartoma
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* Gene: * Chromosome: * Nervous system: * Others:
Li-Fraumeni Syndrome * Gene: TP53 * Chromosome: 17p13 * Nervous system: * astrocytomas * PNET * Others: * breast ca * bone and soft tissue sarcoma * adrenocortical ca * leukaemia
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* Gene: * Chromosome: * Nervous system: * Others:
Turcot Syndrome * Gene: APC * Chromosome: 5q21 * Nervous system: * medulloblastoma * Others: * colorectal polyps * Gene: hMLH1 * Chromosome: 3p21 * Nervous system: * glioblastoma * Others: * colorectal polyps * hPSM
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* Gene: * Chromosome: * Nervous system: * Skin: * Others:
Gorlin Syndrome (Naevoid Basal Cell Carcinoma Syndrome) * Gene: PTCH * Chromosome: 9q22.3 * Nervous system: * medulloblastoma * Skin: * multiple basal cell carcinomas * palmar and plantar pits * Others: * jaw cysts * ovarian fibroma * skeletal abnormalities
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* Gene: * Chromosome: * Nervous system: * Others:
Von Hippel-Lindau * Gene: VHL * Chromosome: 3p25 * Nervous systme: * hemangioblastoma * Others: * retinal hemangiolastoma * renal cell carcinoma * pheochromocytoma * visceral cysts * Immunostain: inhibin and CD10
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Gene: Chromosome: Nervous system: Skin: Others:
Tuberous Sclerosis * Gene: TSC1 and TSC2 * Chromosomes: 9p34 and 16p13 * Nervous system: * subependymal giant cell astrocytoma * subependymal nodules * cortical tubers * Skin: * cutaneous angiofibroma * subungual fibroma * fibrous hamartoma * hypopigmented macule * shagreen patch * Others: * cardiac rhabdomyoma * adenomatous polyps of the duodenum and the small intestine * cysts of the lung and kidney * lymphangioleiomyomatosis * renal angiomyolipoma
50
Gene: Chromosome: Nervous system: Skin: Others:
Tuberous Sclerosis * Gene: TSC1 and TSC2 * Chromosomes: 9p34 and 16p13 * Nervous system: * subependymal giant cell astrocytoma * subependymal nodules * cortical tubers * Skin: * cutaneous angiofibroma * subungual fibroma * fibrous hamartoma * hypopigmented macule * shagreen patch * Others: * cardiac rhabdomyoma * adenomatous polyps of the duodenum and the small intestine * cysts of the lung and kidney * lymphangioleiomyomatosis * renal angiomyolipoma
51
Gene: Chromosome: Nervous system: Skin: Others:
Tuberous Sclerosis * Gene: TSC1 and TSC2 * Chromosomes: 9p34 and 16p13 * Nervous system: * subependymal giant cell astrocytoma * subependymal nodules * cortical tubers * Skin: * cutaneous angiofibroma * subungual fibroma * fibrous hamartoma * hypopigmented macule * shagreen patch * Others: * cardiac rhabdomyoma * adenomatous polyps of the duodenum and the small intestine * cysts of the lung and kidney * lymphangioleiomyomatosis * renal angiomyolipoma
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Gene: Chromosome: Nervous system: Skin: Others:
Cowden Syndrome * Gene: PTEN * Chromosomes: 10q23 * Nervous system: * dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos) * megalencephaly * Skin: * multiple trichilemmoma * fibroma * Others: * hamartomatous polyps of the colon * thyroid neoplasms * endometrial cancers * breast carcinoma
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