Chapter 27 Flashcards
3 common types of peripheral nerve sheath tumors
schwannoma, neurofibroma, MPNST (malignant peripheral nerve sheath tumor)
Peripheral nerve sheath tumor unique features
associated with common familial tumor syndrome (NF1, NF2, schwannomatosis)
MPNSTs seen in context of NF 1–arise through malignant transformation of benign plexiform neurofibromas
What are schwannomas?
Benign tumors with schwann cell diff
Often arise directly from peripheral nerves
Consistent findings in all schwannomas?
Loss of expression of NF2 gene products–merlin
merlin–normally restricts the cell-surface expression of Growth Factor receptors through interactions with actin cytoskeleton
without merlin–cells hyperproliferation in response to growth factors
Schwannoma morphology
well-circumscribed, encapsulated mass next to the associated nerve without invading
Schwannomas dense areas
Antoni A
dense, eiosinophilic
contain spindle cells
schwannomas–loose areas
Antoni B
hypocellular
spindle cells are spread apart by myxoid extracellular matrix
schwannomas–clininical features/symptoms
symptoms caused by local compression of nerve or adjacent structures
- most occur at cerebellopontine angle, attached to vestibular branch of CN8
- tinnitus, hearing loss
- acoustic neuroma
- sensory nerves are preferentially involved–branches of CN5 and dorsal roots
What are neurofibromas?
Benign n sheath tumors–more heterogenous in composition than shwannomas
- neoplastic schwann cells are mexed with perineural-like cells, fibroblasts, mast cells, CD34+ spindle cells
- may be sporadic or NF1 associated
3 types of neurofibromas
superficial cutaneous
diffuse
plexiform
Pathogenesis of neurofibromas
schwann cells–complete loss of NF1 gene product (neurofibromin)
neurofibromin–tumor suppressor–inhibits RAS by stimulating GTPase
Which neurofibromas transform to MPNST (malignant peripheral nerve sheath tumor)?
plexiform neurofibromas
Localized cutaneous neurofibroma morphology
- small, unencapsulated nodular lesions that arise in dermis and subcutaneous fat
- schwann cells mixed with stromal cells
Diffuse neurofibroma morphology
- diffusely infiltrates the dermis and subcutaneous CT–entraps fat and appendage structures–produces a plaque like appearance
- pseudo-Meissner corpuscles/tactile like bodies
Plexiform neurofibroma morphology
- grow within and expand n fascicles, entrapping associated axons
- external perineural layer of nerve is preserved
- expanded, ropy thickening of muliple neuron fascicles–“bag of worm” appearance
- can progress to MPNST
MPNST (malignant peripheral n sheath tumor)–what are they?
85% are high grade tumors
1/2 arise in NF1 patients and result from malifnant transformation of a plexiform neurofibroma
-associated with larger peripheral nerves (in chest, abdomen, pelvis, back, limb-girdle)
-complex chromosomal aberrations
MPNST-morphology
- poorly defined masses, infiltrate along the axis of parent nerve and invade adjacent soft tissues
- appears “marbleized” due to variations in cellularity
- “divergent differentiation”–focal areas that exhibit other lines of differntiation
triton tumor
MPNST
exhibits rhabdomyoblastic morphology
MPNST clues
diagnosis of NF1 in patient
Neurofibromatosis type 1–what is it?
- Autosomal dominant
- Associated with non-neoplastic manifestations and a variety of tumors
- Loss of function in NF1 gene–lack neurofibromin–RAS remains in active state
NF1 symptoms/clinincal presentation
- mental retardation or seizures
- Lisch nodules (pigmented nodules of iris)
- cafe au lait spots
- variety of tumors
NF-2 what is it?
- Autosomal dominant
- range of tumors–most commonly bilateral 8-n schwannomas and meningiomas
- NF2 gene mutated-merlin-cytoskeletal protein-reg membrane R signaling
NF-2 clinical presentation?
- most commonly bilateral 8-n schwannomas and meningiomas
- neoplastic lesions-nodular ingrowth of schwann cells into spinal cord, meningioangiomatosis, glial hamartia
