PNS/Familial/Other Tumors Flashcards
Schwannomas
Definition
Epidemiology
Locations and associated symptoms
Imaging
Benign tumor composed of Schwann cells
Epidemiology - Most common 4th to 6th decades
Involve peipheral nerves
Usually in head and neck and flexor surfaces of extremities
Asymptomatic masses
Spinal tumors – radicular pain
Intracranial tumors – Cerebellopontine angle and attached to 8th nerve
Symptoms of hearing loss, tinnitus, facial numbness
Imaging: Scans show well-defined contrast enhancing mass
What is this?
What does the microscopy look like?
Vestibulocochlear Schwannomas
Neurofibroma
Definition
Association
Forms
Benign tumor composed of Schwann cells, fibroblasts, and perineural cells
Associated with NF type 1
Cutaneous (localized) neurofibroma: Most common
In dermis or subdermal
Usually solitary (not associated with NF1)
Peripheral nerve
Solitary
Plexiform – usually in NF1
What is the pathology of neurofibroma?
Hypocellular, elongated spindle cells with wavy nuclei
Diffusely infiltrate adjacent nerve & soft tissue
What is a plexiform neurofibroma?
What does it affect?
What is the malignant potential?
Transformation of multiple fascicles of nerves into NFoma, with preservation of anatomic configuration (Exclusively NF1)
Typically affect larger nerves or a plexus
High likelihood of malignant transformation
Where do malignant schwannomas affect?
What are they associated with?
What is the pathology?
Mostly extremites
CNS, associated with trigeminal nerve
Strong assoc. with NF1
Pathology
High grade, aggressive
Infiltrative, non-encapsulated felshy masses
Highly cellular, moderate to marked nuclear pleomorphism
High mitotic rate
NF1 - von Recklinghausen disease
Genetics
Epidemiology
Criteria
Genetics – AD
Almost complete penetrance
50% are new mutations
Neurofibromin - NF1 gene on Chromosome 17
GPCR dependent signal transduction pathway (tumor suppressor gene)
Abundant in Schwann cells and neurons
Epidemiology: 1/3000
Much more common than NF2
Criteria
Neurofibromas
Café-au-lait spots
Lisch nodules – Pigmentd hamartomas in iris
Optic glioma
Osseous lesions
Axillary freckling
Family history
What tumors are associated with NF1?
Neurofibromas (all types)
Most important are those that undergo transformation to malignant peripheral nerve sheath tumors
Optic nerve gliomas, other astrocytomas
Others – Rhabdomyosarcomas, pheochromocytomas, carcinoid tumors
NF2
Genetics
Epidemiology
Criteria
Genetics - AD
50% sporadic
Merlin product – Chr. 22
Tumor suppressor which promotes assembly of cell junctions
Loss of gene ruins cell-to-cell contact
Epidemiology: 1/40,000-50,000
Criteria
Bilateral vestibular schwannomas (most common manifestation)
Other associated tumors (meningiomas, schwannomas, gliomas, neurofibromas)
No plexiform NFoma and malignant transformation is rare
von Hippel Landau
Genetics
Epidemiology
Features
Genetics – AD
VHL gene – Chromosome 3
Controls angiogenesis through regulation of expression of EGF, EPO, and other GFs
Epidemiology
1/30,000-40,000
Features
Hemangioblastomas of CNS & retina: Cerebellar hemangioblastomas (25% in VHL, 75% sporadic)
Renal cell carcinoma
Pheochromacytoma
Pancreas, liver, kidney cysts
Retinal angiomas
Tuberous Sclerosis
Genetics
Epidemiology
Clinical S/S
Genetics: AD
Positive family history in 50%
TS caused by mutations in 2 tumor suppressor genes
TSC1 (Chr. 9) – Codes protein hamartin
TSC2 (Chr. 16) – Codes protein tuberin
Dimerize to regulate protein synthesis, cell proliferation (inhibit mTOR)
Epidemiology: 1 in 6000
Clinical S/S: Seizures, autism, cognitive dysfunction
Pathologic changes of tuberous sclerosis
Cortical hamartomas (tubers) Neurons haphazardly arranged in cortex Often have glial as well as neuronal features
Subependymal nodules – Tuber-like
Subcortical glioneuronal hamartomas
Subependymal giant cell astrocytomas
Large pleomorphic multinucleated tumor cells with eosinophilic cytoplasm
Astrocytic/glioneuronal origin
No malignant transformation or local invasion
Other – cutaneous angiofibromas, subungual fibromas, cardiac rhabdomyomas, renal angiomyolipomas, retinal hamartomas, etc.
Hemangioblastoma
Location
S/S
Imaging
Treatment
Cellular origin
Pathology
Most commonly cerebellar
Can be cerebral or spinal
S/S: Secondary to increased ICP due to obstruction
Imaging: MRI shows well defined contrast enhancing cystic mass with mural nodule (right)
Tx: Surgical resection
Grade 1 have rare reports of recurrence
Cellular origin unknown
Pathology: Numerous vessels, interspersed with stromal cells; abundant foamy (lipid) cytoplasm
Definition paraneoplastic syndromes
Syndrome produced by remote effect of a systemic malignancy that cannot be attributed to direct invasion by tumor or its metastasis, infection, ischemia, related metabolic/nutritional disorders, or toxic effects of therapy
Who is at risk for neurologic paraneoplastic syndromes?
0.1% of all cancer patients, 3% of Small Cell Lung Cancer patients (SCLC)
Strong female predominance
What is subacute cerebellar ataxia?
What cancers are associated with it?
What causes the disease?
Progressive ataxia, dysarthria, nystagmus, vertigo, diplopia, titubation
Ovarian cancer (80%) or breast cancer (10%)
Purkinje cell antibodies (PCA-1 or anti-Yo)
What are the S/S of Lambert-Eaton myasthenic syndrome?
What is the pathogenesis?
What is it associated with?
S/S: Muscle weakness (legs), improves with testing on exam
Extraocular sparing
Ab to P/Q-type voltage-gated Ca2+ channels
Decreased ACh release
SCLC associated
What are the other most common paraneoplastic syndromes?
Limbic encephalitis
Encephalomyelitis
Opsoclonus myoclonus
Subacute sensory neuronopathy
What is the presentation of paraneoplastic syndrome?
Subacute worsening over weeks to months
May be presenting symptom of underlying malignancy
Initial cancer screening may be negative
Malignancy at limited stage due to effective anti-tumor immune response
More favorable oncological outcome
What is the pathogenesis for paraneoplastic syndromes?
Hypothesized that some visceral cancers express certain neural antigens
Immune response to antigens
Antibodies identified in some paraneoplastic syndromes
Induced against tumor cell antigens
Cross-react with neuronal cell antigens
