Chapter 28 part 7

Question 1

Primary germ cell tumors–where? when?

Answer 1

midline–pineal and suprasellar regions

• first two decades
• metastasis of a gonadal germ cell tumor to the CNS is common
• CSF levels- alpha-fetoprotein, B-HCG

Question 2

pineal parenchymal tumors–range from? who?

Answer 2

• arise from specialized cells of pineal gland
• range from well-differentiated lesions (pineocytomas) to high-grade tumors (pineoblastoma)
• high grade pineal tumors–children–mutations in RB
• low grade lesions-adults

Question 3

meningiomas–what are they? risk factor? spread how?

Answer 3

• benign tumors of adults, usually attached to dura, that arise from the meningothelial cells of the arachnoid
• uncommon in children; more common in females
• prior radiation therapy to head and neck
• en plaque- tumor spreads in sheetlike fashion- grade 1

Question 4

meningiomas- genetics

Answer 4

• loss of chromosome 22 (NF2 gene- merlin)
• sporadic- 50% have mutations in NF2- higher grade
• other common mutations- TRAF7 (TNF-R associated factor)- lower grade

Question 5

meningiomas- histologic patterns

Answer 5

• syncytial
• fibroblastic
• transitional
• psammomatous
• secretory
• microcystic

Question 6

atypical meningiomas

Answer 6

Grade II

• higher rate of occurrence, more aggressive local growth
• clear cell and chordoid histologic patterns

Question 7

anaplastic (malignant) meningioma

Answer 7

Grade III

-highly aggressive

Question 8

metastatic tumors- mostly? 5 most common sites

Answer 8

• mostly carcinomas (25-50% of intracranial tumors)

- lung, breast, skin, kidney, GI tract

Question 9

metastatic tumors- morphology

Answer 9

• boundary bw tumor and brain parenchyma well-defined
• nodules of tumor-central areas of necrosis, surrounded by reactive gliosis
• meningeal carcinomatosis- associated with carcinoma of lung and breast

Question 10

paraneoplastic syndromes–mechanism?

Answer 10

-development of an immune response against tumor antigens– cross react with age in central or peripheral nervous system

Question 11

subacute cerebellar degeneration

Answer 11

• destruction of purkinje cells, gloss, chronic inflammatory infiltrate
• circulating PCA-1 ab (anti-Yo) recognizes cerebellar purkinje cells
• in women with ovarian, uterine, breast carcinoma

Question 12

Limbic encephalitis

Answer 12

• subacute dementia, perivascular inflammatory cuffs, microglial nodules, neuronal loss, gliosis
• ANNA-1 ab (anti-hu)- neuronal nuclei in CNS/PNS (small cell carcinoma of lung)
• ab that recognizes NMDA R- cross reacts with hippocampal neurons (ovarian teratomas)
• appears before any malignancy is suspected

Question 13

eye movement disorder associated with?

Answer 13

neuroblastoma in kids

Question 14

subacute sensory neuropathy

Answer 14

-loss of sensory neurons from dorsal root ganglia

Question 15

lambert-eaton myasthenic syndrome

Answer 15

Abs against voltage gated Ca channel in presynaptic elements of NMJ

Question 16

Bowden syndrome

Answer 16

• mutations in PTEN (P13K/AKT signaling pathway)

- dysplastic gangliogliocytoma of cerebellum

Question 17

Li-Fraumeni syndrome

Answer 17

• medulloblastomas

- mutations in TP53

Question 18

Turcot syndrome

Answer 18

medulloblastoma, glioblastoma

-mutations in APC or mismatch repair genes

Question 19

Goblin syndrome

Answer 19

• medulloblastoma

- mutation PTCH gene (SHH signaling)

Question 20

Tuberous sclerosis complex-clinical genes?

Answer 20

• autosomal dominant
• development of hamartomas and benign neoplasms
• clinical- seizures, autism, mental retardation
• TSC1 (hamartin)
• TSC2 (tubers)- more common
• these 2 inhibit kinase mTOR (key regulator or protein synthesis, cell size)
• voluminous amounts of cytoplasm

Question 21

Tuberous Sclerosis Complex morphology

Answer 21

• cortical hamartomas- like potatoes (tubers)- firm areas of cortex
• cells stain for tubers, hamartin

Question 22

Von Hippel- Lindau Disease- what is it? Gene?

Answer 22

• Autosomal dominant
• hemangioblastomas of CNS and cysts in pancreas, liver, kidneys; renal cell carcinoma and pheochromocytoma
• VHL (tumor suppressor gene)- down regulate HIF-1

Question 23

Von- Hippel Lindau Disease morphology

Answer 23

• hemangioblastomas- highly vascular neoplasms- fluid filled cyst
• second hit in VHL allele

Question 24

Neurofibromatosis

Answer 24

-2 autosomal dominant disorders- NF1 and NF2

Question 25

NF1

Answer 25

More common

• neurofibromas of peripheral n
• gliomas of optic n
• Lisch nodules (pigmented nodules of iris)
• cafe au last spots (cutaneous hyper pigmented macule)

Question 26

NF2

Answer 26

• bilateral schwannomas of CN8 and multiple meningiomas

- gliomas may occur–ependymomas of spinal cord