Chapter 27: Peripheral Nerves and Skeletal Muscles

Question 1

Are Schwannomas bening or malignant?

Answer 1

Benign

Question 2

Expression of what gene product is lost in ALL Schwannomas?

Answer 2

NF2 gene product, merlin

Question 3

Having ____________ is virtually pathognomonic for NF2?

Answer 3

Bilateral Schwannomas

Question 4

Immunoreactivity for S-100 is associated with what type of tumor?

Answer 4

Schwannoma

Question 5

What is the morphological characteristics of Schwannomas?

Answer 5

• Well-circumscribed, encapsulated masses that abut the associated nerve, but do not invade, allowing surgical excision

Question 6

Presence of a spingled, elongated nucleus with wavy or buckled shape is characteristic of what cell type?

Answer 6

Schwann cell

Question 7

Verocay bodies are associated with what type of tumor?

Answer 7

Schwannomas

Question 8

Inside the cranial vault, Schwannomas occur at the ___________ angle, where they attach to what?

Answer 8

Cerebellopontine angle, attached to the vestibular branch of CN VIII

Question 9

What is the common clinical presentation of someone with a Schwannoma?

What is the prognosis?

Answer 9

• Present with tinnitus and hearing loss –> tumor known as acoustic neuroma
• May also involve trigeminal nerve and dorsal roots
• Surgical removal is curative; recurrence unlikely

Question 10

Which tumor is commonly referred to as an Acoustic Neuroma?

Answer 10

Schwannoma

Question 11

Neurofibromas are ________ tumors.

Answer 11

Benign

Question 12

How do Neurofibromas differ from Schwannomas?

What’s their composition?

Answer 12

• More heterogenous
• Neoplastic Schwann cells admixed with perineural like cells, fibroblasts, mast cells, and CD34+ spindle cells

Question 13

Differentiate Superficial cutaneous, Diffuse, and Plexiform Neurofibromas?

Answer 13

• Superficial cutaneous: present as pedunculated nodules that can be seen isolated (if sporadic) or mutiple (if NF-1 associated)
• Diffuse: present as large plaquelike elevation of skin and usually NF-1 associated
• Plexiform: found in deep or superficial locations in association w/ nerve roots or large nerves and are uniformly NF-1 associated

Question 14

Schwann cells in Neurofibromas show complete loss of NF1 gene product, neurofibromin, what is the normal function of this gene product?

Answer 14

Tumor suppressor that inhibits RAS by stimulating GTPase

Question 15

Which subtype of neurofibromas can potentially transform into a malignant peripheral nerve sheath tumor (MPNST)?

Answer 15

Plexiform neurofibroma

Question 16

Pseudo-Meissner corpuscles or tactile-like bodies are seen with what tumor?

Answer 16

Diffuse neurofibroma

Question 17

Small unencapsulated nodular lesions arising in the dermis and subcutaneous fat is associated with what type of tumor?

Answer 17

Localized cutaneous neurofibroma

Question 18

NF1-haploinsufficient mast cells are hypersensitive to _______ ligand produced by Schwann cells and in reponse secrete factors stimulating Schwanna cell growth

Answer 18

KIT

Question 19

Malignant Peripheral Nerve Sheath Tumors (MPSNT) are considered what grade and which patients do they often arise in?

Answer 19

• 85% are HIGH grade
• Half arise from NF1 patients and assumed to result from malignant transformation of plexiform neurofibromas

Question 20

What is the typical morphology of MPNSTs?

Answer 20

• Poorly defined w/ mitoses, necrosis, and nuclear anaplasia
• Fasciculated arrangement of spindle cells
• Appear “marbleized”

Question 21

What is “divergent differentiation” in terms of MPNSTs?

Answer 21

Presence of focal areas of differentiation, including glandular, cartilaginous, osseous, or rhabdomyoblastic morphology

Question 22

What is a Triton tumor?

Answer 22

A MPNST with “divergent differentiation” –> focal areas of glandular, cartilaginous, osseous, and rhabdomyoblastic morphology

Question 23

MPNSTs are often hard to differentiate from what other tumor type; what is helpful in making the distinction?

Answer 23

• Sarcomas
• Diagnosis of NF1 in affected patient is helpful + clearly demonstrated anatomic relationship to a nerve or to a preexisting neurofibroma

Question 24

Inheritance pattern of NF1 and disease caused by loss of NF1 gene on which chromosome?

Answer 24

• Autosomal dominant
• NF1 gene, located at 17q11.2

Question 25

Tumors associated with NF1?

Answer 25

• MPNST
• Glioma of optic nerve
• Hamartomatous lesions
• Pheochromocytomas

Question 26

Presentation/common findings in patient with NF1?

Answer 26

• Mental retardation or seizures
• Skeletal defects
• Lisch nodules: pigmented nodules of iris
• Cafe-au-lait spots: cutanous hyperpigmented macules

Question 27

Inheritance pattern of NF-2 and what chromosome is the NF2 gene found on?

Answer 27

• Autosomal dominant
• Chromosome 22

Question 28

What 3 tumors are commonly associated with NF2?

Answer 28

1) Bilateral CN VIII schwannomas
2) Multiple meningiomas
3) Gliomas (ependymomas of the spinal cord)

Question 29

Which 3 non-neoplastic lesions are associated with NF2?

Answer 29

1) Schwannosis: nodular ingrowth of schwann cells into spinal cord
2) Meningioangiomatosis: proliferation of meningeal cells and blood vessels that grow into brain
3) Glial hamartia: microscopic nodular collections of glial cells at abnormal locations (superficial or deep cerebral cortex)

Question 30

Function of the NF2 gene product Merlin?

Answer 30

Cytoskeletal protein that regulates membrane receptor signaling