Are Schwannomas bening or malignant?
Expression of what gene product is lost in ALL Schwannomas?
NF2 gene product, merlin
Having ____________ is virtually pathognomonic for NF2?
Immunoreactivity for S-100 is associated with what type of tumor?
What is the morphological characteristics of Schwannomas?
- Well-circumscribed, encapsulated masses that abut the associated nerve, but do not invade, allowing surgical excision
Presence of a spingled, elongated nucleus with wavy or buckled shape is characteristic of what cell type?
Verocay bodies are associated with what type of tumor?
Inside the cranial vault, Schwannomas occur at the ___________ angle, where they attach to what?
Cerebellopontine angle, attached to the vestibular branch of CN VIII
What is the common clinical presentation of someone with a Schwannoma?
What is the prognosis?
- 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
Which tumor is commonly referred to as an Acoustic Neuroma?
Neurofibromas are ________ tumors.
How do Neurofibromas differ from Schwannomas?
What’s their composition?
- More heterogenous
- Neoplastic Schwann cells admixed with perineural like cells, fibroblasts, mast cells, and CD34+ spindle cells
Differentiate Superficial cutaneous, Diffuse, and Plexiform Neurofibromas?
- 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
Schwann cells in Neurofibromas show complete loss of NF1 gene product, neurofibromin, what is the normal function of this gene product?
Tumor suppressor that inhibits RAS by stimulating GTPase
Which subtype of neurofibromas can potentially transform into a malignant peripheral nerve sheath tumor (MPNST)?
Pseudo-Meissner corpuscles or tactile-like bodies are seen with what tumor?
Small unencapsulated nodular lesions arising in the dermis and subcutaneous fat is associated with what type of tumor?
Localized cutaneous neurofibroma
NF1-haploinsufficient mast cells are hypersensitive to _______ ligand produced by Schwann cells and in reponse secrete factors stimulating Schwanna cell growth
Malignant Peripheral Nerve Sheath Tumors (MPSNT) are considered what grade and which patients do they often arise in?
- 85% are HIGH grade
- Half arise from NF1 patients and assumed to result from malignant transformation of plexiform neurofibromas
What is the typical morphology of MPNSTs?
- Poorly defined w/ mitoses, necrosis, and nuclear anaplasia
- Fasciculated arrangement of spindle cells
- Appear “marbleized”
What is “divergent differentiation” in terms of MPNSTs?
Presence of focal areas of differentiation, including glandular, cartilaginous, osseous, or rhabdomyoblastic morphology
What is a Triton tumor?
A MPNST with “divergent differentiation” –> focal areas of glandular, cartilaginous, osseous, and rhabdomyoblastic morphology
MPNSTs are often hard to differentiate from what other tumor type; what is helpful in making the distinction?
- Diagnosis of NF1 in affected patient is helpful + clearly demonstrated anatomic relationship to a nerve or to a preexisting neurofibroma
Inheritance pattern of NF1 and disease caused by loss of NF1 gene on which chromosome?
- Autosomal dominant
- NF1 gene, located at 17q11.2
Tumors associated with NF1?
- Glioma of optic nerve
- Hamartomatous lesions
Presentation/common findings in patient with NF1?
- Mental retardation or seizures
- Skeletal defects
- Lisch nodules: pigmented nodules of iris
- Cafe-au-lait spots: cutanous hyperpigmented macules
Inheritance pattern of NF-2 and what chromosome is the NF2 gene found on?
- Autosomal dominant
- Chromosome 22
What 3 tumors are commonly associated with NF2?
1) Bilateral CN VIII schwannomas
2) Multiple meningiomas
3) Gliomas (ependymomas of the spinal cord)
Which 3 non-neoplastic lesions are associated with NF2?
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)
Function of the NF2 gene product Merlin?
Cytoskeletal protein that regulates membrane receptor signaling