CNS Tumors

Question 1

WHO Grading

Answer 1

I: Curable with resection
II: Resection may not be curative (7-10yr expect)
III: NOT surgically curable. Can kill as III or IV (3-7yr)
IV: NOT surgically curable. Kills in 12-18mo.

Question 2

Gliomas

Answer 2

Tumors arising from glial cells

• astrocytomas
• oligodendrogliomas
• ependymomas

Question 3

Pilocytic Astrocytoma

Answer 3

Usually benign astrocytic tumor
-Mostly kids
-Supracellar or cerebellar
Diagnostic:
-MRI: Cyst with Mural Nodule
-Rosenthal Fibers (thick eosinophilic astrocyte processes full of tumor protein), hairlike cell projections
-GFAP + (since GFAP = astrocyte stain)

Question 4

Diffuse Astrocytoma

Answer 4

WHO II-IV

• unlike pilocytic, diffuse can be anywhere in brain
• GFAP +
• Irregular, elongated crowded dark nuclei on almost solid pink background (fibers everywhere). See astrocytes not adhering to boundaries, overgrowing each other

Question 5

Diffuse Astrocytoma Grades

Answer 5

II-IV
II: Astrocytic Neoplasm. Minimal atypia
III: Anaplastic Astrocytoma- hypercellular, mitotic activity
IV: Glioblastoma: III features + microvascular proliferation, palisading necrosis

Question 6

Glioblastoma

Answer 6

Grade IV Diffuse astrocytoma

• See ring enhanced lesion- dark interior, white ring around edge, edema around that. Dark from palisading necrosis inside, white from mitotic cells surrounding.
• Butterfly Lesion: on gross anatomy, tumor crosses corpus colossum
• Microvascular Proliferation: thick abnormal capillaries
• Palisading Necrosis: tumor outgrows blood supply so interior dies, but active cells gather around edge
• GFAP +

Question 7

MGMT

Answer 7

protein examined in glioblastoma

• key to DNA repair, also prevents temozolomide function (chemo for glioblastoma)
• Promoter methylation prevents MGMT mRNA production, so good for treatment and increased survival

Question 8

Oligodendroglioma

Answer 8

-Oligodendrocyte neoplasm
-grade II-III
-Found in cerebral hemisphere (frontal)
-hemorrhagic, can present with seizures
-From co-deletion of 1p + 19q
Hallmark:
-“Fried Egg nuclei”: unlike usual neat lines with neat small white around dark nuclei, see many haphazard packed cells with lighter messier nuclei and larger, messier white area (like fried egg)
-“Chickenwire Vasculature”: see vascularization in pattern of chicken wire (hexagon fence links)
-Calcification: see dark purple calcification

Question 9

Ependymoma

Answer 9

Tumor of ependymal cells (CSF producing)

• Grade II-III
• Can be anywhere with ependyma (ventricles/SC), but ventricles more in kids and aggressive
• See clearing around vessels and pseudorosettes (“snorkels” for tumor cells to reach blood supply)
• Might have hydrocephalus

Question 10

Pituitary Adenoma

Answer 10

Low grade neuroendocrine tumor
-Often null (no hormone production). Most common hormone-producing is prolactinoma
Symtoms: bitemporal hemianopsia (since overlies optic chiasm), amenorrhea/lactation (prolactinoma), acromegaly (GH), Cushing’s Disease (ACTH)

Question 11

Craniopharyngioma

Answer 11

Tumor of young kids
-from derivative of Rathke’s pouch (mouth evagination to make pituitary)
-Found supratentorial, can cause bitemporal hemianopsia
Hallmark:
-“Wet keratin”: looks like pink layered fat caterpillar
-“Cholesterol Clefts”: long lens-shaped artifacts from dissolving fat
-calcification

Question 12

Neurofibromatosis Type I

Answer 12

Mutation in NF1 gene prevents neurofibromin production–>No Ras inhibition–>cancer

• Neurofibromas: PNS nerve sheath tumor, see hundreds like pustules across skin
• Cafe au lait spots: looks like coffee spill on skin
• Optic Gliomas:
• Pheochromocytomas:
• Malignant peripheral nerve sheath tumor

Question 13

Neurofibromatosis Type II

Answer 13

NF2 gene codes for Merlin protein, links membrane proliferation to cytoskeleton- lack causes uncontrolled growth
CNS tumors:
-Bilateral Vestibular Schwannoma (hallmark) or vestibular n.
-Meningiomas
-Ependymomas

Question 14

Schwannoma

Answer 14

Schwann cell tumor
-Grade I
-Can occur anywhere in PNS, symptoms depend on nerve compressed
-Many due to biallelic NF2 inactivation
-In Neurofibromatosis Type II, get bilateral vestibular schwannomas- deafness, tinnitus
Hallmark:
-Antoni Type I & II areas (hyper/hypocellular areas)
-Verocay Bodies: nuclei line up together in rows
-Tumors are S-100 + (marker for neural crest cell origin)

Question 15

Meningioma

Answer 15

Dural-based meningeal tumor
-Grades I-III
-50% have NF2 mutation
Hallmark:
-MRI shows “Dural tail” (bell curve appearance, tails extend along dura)
-Whorls: “starry night” type whirls of indistinct tumor cells
-Psammomatous calcifications: layers of pink/purple calcification like onion, dark red dot in middle

Question 16

Tuberous Sclerosis Complex

Answer 16

Mutation in TSC1/TSC2 protein- regulates mTOR, lack allows cancer
CNS lesions:
-Cortical Tubers:
-SEGA (subependymal giant cell astrocytoma): tumors bulge into ventricles, block CSF outflow
Other organs
-Renal angiomyolipomas:
-Pulmonary
-Dermal angiofibroma

(so if ventricular tumors, renal issues, think TSC

Question 17

Von Hippel Landau

Answer 17

Mutation in VHL gene (chromosome 3) causes constitutive HIF activation, uncontrolled angiogenesis
See:
-Hemangioblastoma: grade I cerebellum>spine/brainstem/retina, foamy stromal cells + dense capillary network
-Renal cell carcinoma
-Pheochromocytoma
-Retinal angioma
-Skin, organ hemangioma

Question 18

Medulloblastoma

Answer 18

Malignant PCF/cerebellar tumor of primitive neurons

• Grade IV, kids
• Synaptophysin +
• True Tumor Rosettes (center is tumor, not normal structure like bv)

Question 19

CNS Metastasis

Answer 19

More likely incoming>outgoing
-most common lung, breast most correlated breast/renal/melanoma
-Find at grey-white juncture (best circulation)
-Perfectly round/pigmented, unlike astrocytomas
So if find multiple round CNS tumors at grey-white junction in patient with another cancer, prob metastasis