NEURO 4 Flashcards
What are the three common nerve sheath tumors
Schwannomas, neurofibromatosis, and malignant peripheral nerve sheath tumor (MPNST)
Schwannomas
Encapsulated , benign tumors that can be associated with NF2
Pathogenic sign for NF2
Bilateral acoustic schwannnomas is virtually pathogenic
Neurofibromatosis
Benign peripheral nerve sheath tumors sometimes associated with NF1
- localized
- cutaneous
- plexiform
It is though the __ is a malignant transformation of plexiform neurofibroma
MPNST
MPNST
Can be de novo sporadic neoplasms of NF1 associated tumors arising through malignant transformation of a plexiform neurofibroma
Schwannomas
Benign tumors with Schwann cell differentiation that arise directly from peripheral nerves
Forms of schwannoma
NF2 and sporadic forms are associated with NF2 gene mutation on chromosome 22
What does NF2 gene code for
Merlin, which normally restricts cell surface expression of GF receptors via interactions with the actin cytoskeleton
Schwannoma absence of Merlin
Hyperproliferation of cells in response to gF
Schwann cell origin
Borne out by their uniform immureactivity for s-100
S for schwann
Morphology schwannoma
Well circumscribed, encapsulated masses that abut the nerve but do not invade it, allowing surgical excision-benign
Antoni A areas schwannoma
Admixture of dense areas containing spindle cells in intersecting fascicles and Verocay bodies
Verocay bodies
Nuclear free zones between pulsating nuclei
Antoni b areas
Admixture of loose areas (hypocellular) spindle cells are spread apart by extracellular matrix (may be associated with microcyst formation)
Schwann cells
Presence of spindled, elongated nucleus with a wavy or buckled shape
Presentation schwannomas
Signs and symptoms due to compression of the involved nerve or adjacent structures (brainstem or spinal cord
Tinnitus and hearing loss
Cranial vault schwannoma
Tumors are seen at the cerebellopontine angle (attached to vestibular branch of CNVIII vestibular branch)
Acoustic neuroma
Double misnomer. Neighbor a neuroma nor does it arise from acoustic part of nerve
What other nerves can schwannomas appear
Sensory (trigeminal and dorsal)
Extramural schwannoma
Associated with large nerve trunks or as soft tissue lesions without an associated nerve
Treatment schwannoma
Surgery
Neurofibroma
Benign, nerve sheath tumors with a more heterogenous composition than schwannomas
What are neufibromas derived from
Schwann cell lineage
Neoplastic Schwann cells are admired with what
Perineurial like cells, fibroblasts, mast cells, CD34 spindle cells
Cause of neurofibroma
Sporadic of NF1 associated
Superficial cutaneous growth pattern neurofibroma
Pedunculated nodules (isolated-sporadic, multiple-NF1)
Diffuse growth pattern neurofibroma
Large, plaque like elevation of skin NF1
Plexiform growth of neurofibroma
Seen in deep or superficial locations, associated with nerve roots or large nerves NF1
Rarely transform to MPNST
Pathogenesis neurofibroma
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
Neurofibroma morphology
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
Diffuse neurofibroma morphology
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
Plexiform neurofibroma morphology
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_
Malignant peripheral nerve sheath tumor (MPSNT_
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
Morphology malignant peripheral nerve sheath tumor
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
What aremalignant peripheral nerve sheath tumors hard to differentiate from
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
Triton tumor
Divergent differentiation
Focal areas with lines of differentiation (glandular , cartilaginous, osseous, rhabdomyoblastic)
NF1
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
Mutation NF1
AD
17q NF1 LOF (neurofibromin)
Penetrate of NF1
High
Mosaicism NF1
Patients exhibit only subtitle features or have disease restricted to a certain body part
Presentation NF1
Mental retardation or seizures
Skeletal defects
Lisch nodules-pigmentaed nodules in retina
Cafe au last spots-macular cutaneous hyperpigmentation(virtually pathognomonic)
NF3
Less common than NF1
Presentation of NF2
Bilateral CNVIII schwannomas and multiple meningiomas
Gliomas (ependymomas of the spinal cord) and also occur
NF2 non neoplastic lesions
Schwannomas
Meningioangiomatosis
Glial harmartia
Schwannosis
Nodular ingrowth of schwann cells into the spinal cord
Meningioangiomatosis
Proliferation of meningeal cells and flood vessels growing in the brain
Glial harmartia
Microscopic nodular collections of glial cells at abnormal locations (superficial or dep cerebral cortex)
Mutations NF2
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
