NEURO 4

Question 1

What are the three common nerve sheath tumors

Answer 1

Schwannomas, neurofibromatosis, and malignant peripheral nerve sheath tumor (MPNST)

Question 2

Schwannomas

Answer 2

Encapsulated , benign tumors that can be associated with NF2

Question 3

Pathogenic sign for NF2

Answer 3

Bilateral acoustic schwannnomas is virtually pathogenic

Question 4

Neurofibromatosis

Answer 4

Benign peripheral nerve sheath tumors sometimes associated with NF1

• localized
• cutaneous
• plexiform

Question 5

It is though the __ is a malignant transformation of plexiform neurofibroma

Answer 5

MPNST

Question 6

MPNST

Answer 6

Can be de novo sporadic neoplasms of NF1 associated tumors arising through malignant transformation of a plexiform neurofibroma

Question 7

Schwannomas

Answer 7

Benign tumors with Schwann cell differentiation that arise directly from peripheral nerves

Question 8

Forms of schwannoma

Answer 8

NF2 and sporadic forms are associated with NF2 gene mutation on chromosome 22

Question 9

What does NF2 gene code for

Answer 9

Merlin, which normally restricts cell surface expression of GF receptors via interactions with the actin cytoskeleton

Question 10

Schwannoma absence of Merlin

Answer 10

Hyperproliferation of cells in response to gF

Question 11

Schwann cell origin

Answer 11

Borne out by their uniform immureactivity for s-100

S for schwann

Question 12

Morphology schwannoma

Answer 12

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

Question 13

Antoni A areas schwannoma

Answer 13

Admixture of dense areas containing spindle cells in intersecting fascicles and Verocay bodies

Question 14

Verocay bodies

Answer 14

Nuclear free zones between pulsating nuclei

Question 15

Antoni b areas

Answer 15

Admixture of loose areas (hypocellular) spindle cells are spread apart by extracellular matrix (may be associated with microcyst formation)

Question 16

Schwann cells

Answer 16

Presence of spindled, elongated nucleus with a wavy or buckled shape

Question 17

Presentation schwannomas

Answer 17

Signs and symptoms due to compression of the involved nerve or adjacent structures (brainstem or spinal cord

Tinnitus and hearing loss

Question 18

Cranial vault schwannoma

Answer 18

Tumors are seen at the cerebellopontine angle (attached to vestibular branch of CNVIII vestibular branch)

Question 19

Acoustic neuroma

Answer 19

Double misnomer. Neighbor a neuroma nor does it arise from acoustic part of nerve

Question 20

What other nerves can schwannomas appear

Answer 20

Sensory (trigeminal and dorsal)

Question 21

Extramural schwannoma

Answer 21

Associated with large nerve trunks or as soft tissue lesions without an associated nerve

Question 22

Treatment schwannoma

Answer 22

Surgery

Question 23

Neurofibroma

Answer 23

Benign, nerve sheath tumors with a more heterogenous composition than schwannomas

Question 24

What are neufibromas derived from

Answer 24

Schwann cell lineage

Question 25

Neoplastic Schwann cells are admired with what

Answer 25

Perineurial like cells, fibroblasts, mast cells, CD34 spindle cells

Question 26

Cause of neurofibroma

Answer 26

Sporadic of NF1 associated

Question 27

Superficial cutaneous growth pattern neurofibroma

Answer 27

Pedunculated nodules (isolated-sporadic, multiple-NF1)

Question 28

Diffuse growth pattern neurofibroma

Answer 28

Large, plaque like elevation of skin NF1

Question 29

Plexiform growth of neurofibroma

Answer 29

Seen in deep or superficial locations, associated with nerve roots or large nerves NF1 Rarely transform to MPNST

Question 30

Pathogenesis neurofibroma

Answer 30

Only the schwann cells in neurofibromas show complete loss of NF1 product indicating that these are the neoplastic cells Neurofibromin is a tumor suppressor that inhibits RAS by stimulating GTPase NF1 Haplo-insufficient mast cells are hypersensitized to KIT ligand and respond by producing factors to stimulate schwann cell growth

Question 31

Neurofibroma morphology

Answer 31

Small, well delineated, unencapsulated nodular lesions Arise in dermis and SQ fat-benign nodules int he dermis and SQ fat-neurofibromas Low cellularity and admired with bland schwann cells, stromal cells (mast cells, perineurial cells, CD34 spindle cells, fibroblasts Stroma contains loose collagen Dane also structures may be trapped at the edge of lesions

Question 32

Diffuse neurofibroma morphology

Answer 32

Diffuselyinfiltrates the dermis and SQ CT ``` Entrants fat and appendage structures->plaque like appearance May grow to be large Pseudomeissner corpsules (tactile like bodies) ``` Focal collections of cells mimicking appearance of Meissen corpuscles

Question 33

Plexiform neurofibroma morphology

Answer 33

Plexiform neurofibroma has the potential to transform to a malignant peripheral nerve sheath tumor Grows within and expand the nerve fascicles, entrapping associated axons Ropy thickening of multipl fascicles->bag of wormsapperance External perineurial layer of the nerve is preserved individual nodules appear encapsulated ECM varies from loose/myxoid to collagenous/fibrous Collagen may be seen in bundles (shredded carrots_

Question 34

Malignant peripheral nerve sheath tumor (MPSNT_

Answer 34

85%high grade 50% seen in NF1 patients, result of malignant transformation from plexiform neurofibromas Can also arise de novo and are associated with larger, peripeheral nerves of the chest, abdomen, pelvis, neck or limb girdle

Question 35

Morphology malignant peripheral nerve sheath tumor

Answer 35

Poorly defined tumor masses Infiltrate along the axis of the parent nerve, invading adjacent soft tissue Fasciculations arrangement of spindle cells MARBELIZed appearance due to variation in cellularity )marble like appearance also seen in multicystic encephalopathy) Mitosis, necrosis, and nuclear anaplastic are common

Question 36

What aremalignant peripheral nerve sheath tumors hard to differentiate from

Answer 36

Undifferentiated sarcoma Helpful clues include a diagnosis of NF1 in the affected patient an a clearly demonstrated an atomic relationship to a nerve or to a preexisting (plexiform) neurofibroma

Question 37

Triton tumor

Answer 37

Divergent differentiation Focal areas with lines of differentiation (glandular , cartilaginous, osseous, rhabdomyoblastic)

Question 38

NF1

Answer 38

Systemic disease with non neoplastic manifestations and neurofibromas of all type MPNST, gliomas of the optic nerve, other glial tumors and hamartomatous lesions, pheochromocytoma Had have nodular lesions distorting thing like the face and ears Plexiform architecture

Question 39

Mutation NF1

Answer 39

AD | 17q NF1 LOF (neurofibromin)

Question 40

Penetrate of NF1

Answer 40

High

Question 41

Mosaicism NF1

Answer 41

Patients exhibit only subtitle features or have disease restricted to a certain body part

Question 42

Presentation NF1

Answer 42

Mental retardation or seizures Skeletal defects Lisch nodules-pigmentaed nodules in retina Cafe au last spots-macular cutaneous hyperpigmentation(virtually pathognomonic)

Question 43

NF3

Answer 43

Less common than NF1

Question 44

Presentation of NF2

Answer 44

Bilateral CNVIII schwannomas and multiple meningiomas | Gliomas (ependymomas of the spinal cord) and also occur

Question 45

NF2 non neoplastic lesions

Answer 45

Schwannomas Meningioangiomatosis Glial harmartia

Question 46

Schwannosis

Answer 46

Nodular ingrowth of schwann cells into the spinal cord

Question 47

Meningioangiomatosis

Answer 47

Proliferation of meningeal cells and flood vessels growing in the brain

Question 48

Glial harmartia

Answer 48

Microscopic nodular collections of glial cells at abnormal locations (superficial or dep cerebral cortex)

Question 49

Mutations NF2

Answer 49

AD Chromosome 22q12(Merlin) loss of tumor suppressor Commonly mutate d in sporadic meningiomas and schwannomas NF1 gene is on chromosome 17 Nonsense and frameshift mutations cause more severe phenotypes than miss ensue mutation