Chapter 27: Peripheral Nerve Sheath Tumors

Question 1

What are the major manifestations of Tuberous Sclerosis?

Answer 1

• autosomal dominant

Seizures, autism, and mental retardation

• Hamartomas: cortical tubers
• Renal angiomyoplipomas
• Cardiac rhabdomyomas
• Shagreen patches and Ash-leaf patches

-“candle guttering”: drop-like masses bulge into the ventricles

Question 2

What genes are associated with Tuberous sclerosis complex?

What chromosome are they on?

What protein do they encode for?

Answer 2

• TSC1, Chromosome 9q34, hamartin
• TSC2, Chromosome 16p13.3, tuberin

Question 3

Which hematologic complication may be seen with Von Hippel-Lindau disease?

Answer 3

Polycythemia

Question 4

What chromosome is the NF1 gene located on?

Answer 4

17q11.2 (tumor suppressor neurofibromin)

Question 5

What does NF1 lead to?

Answer 5

neurofibromas of peripheral nerves

optic nerve gliomas

Lisch nodules

Cafe au lait spots

Question 6

What chromosome is the NF2 gene on and what is the gene product?

Answer 6

chromosome 22q12

merlin

Question 7

What is NF2 associated with?

Answer 7

bilaterally schwannomas (CN VIII), multiple meningiomas, ependymomas of spinal cord

Question 8

What is characteristic histology of Schwannoma’s?

Answer 8

• Antoni A areas: spindle cells, Verocay bodies = palisading nuclei around “nuclear free zones”
• Antoni B: hypocellular, myxoid extracellular matrix

Question 9

Where do Schwannomas arise within cranial vault and what are the signs/sx’s?

Answer 9

• Arise cerebellar pontine angle; attached to vestibular branch of CN VIII
• Pt’s present with tinnitus and hearing loss - acoustic neuroma

Question 10

Which gene mutation is a consistent finding in all Schwannomas?

Answer 10

Inactivation of NF2 on Cr. 22 –> loss of Merlin expression

Question 11

Which pattern of Neurofibromas grows within and expands nerve fascicles, entrapping associated axons and is sometimes describes as a “bag of worms?”

Answer 11

Plexiform neurofibromas

Question 12

Which growth pattern of neurofibromas may transform to a malignant peripheral nerve sheath tumor?

Answer 12

Plexiform neurofibroma

Question 13

What is the grade of most malignant peripheral nerve sheath tumors (MPNST) and half arise in which patients?

Answer 13

• 85% are high grade
• Half arise in NF1 pt’s: malignant transformation of plexiform subtype

Question 14

Malignant peripheral nerve sheath tumors (MPNST) that has focal areas exhibiting rhabdomyoblastic morphology are termed what?

Answer 14

Triton tumors

Question 15

What are the manifestations of Neurofibromatosis type I?

Answer 15

• Neurofibromas of peripheral nerves
• Optic nerve gliomas
• Lisch nodules: pigmented nodules of the iris
• Café-au-lait spots

Question 16

What are the common manifestations of Neurofibromastosis type 2?

Answer 16

• Bilateral scwannomas (CN VIII), cerebellopontine angle
• Multiple meningiomas and ependymomas of the spinal cord

Question 17

The NF2 gene is located on which chromosome and what is it’s normal gene product?

Answer 17

NF2 on Cr. 22 –> Merlin (tumor suppressor)