Updated: 3/24/2018

Neurofibroma

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Introduction
  • Benign nerve sheath tumors with multiple cell types
    • fibroblasts (predominant cell)
    • nonmyelinating Schwann cells 
      • cell of origin, arises from this cell
    • perineural cells 
    • differentiate from Schwannoma, which involves Schwann cell alone
  • Molecular biology
    • arise in nonmyelinating Schwann cells with biallelic inactivation of NF1 tumor-suppressor gene
    • loss of expression of protein neurofibromin 
      • neurofibromin negatively regulates RAS-mediated pathway
      • loss of neurofibromin leads to increased RAS activity
      • affects RAS-dependent MAPK activity which is essential for osteoclast function and survival
    • rapid hyperplasia of nonmyelinating Schwann cells into neurofibromas after NF1 inactivation
      • recruits perineural cells, fibroblasts, mast cells, endothelial cells
  Location Inheritance Age group
Sporadic neurofibromas Peripheral PNS tumors of the extremities - 20-40y
Neurofibromatosis (NF1) Tendency to be found near spinal cord/brain (CNS) and uncommon locations (parotid glands, tongue) AD, chr 17q11.2 <20y
 
Classification
 
Subtypes of neurofibroma Origin Description Associations Onset Malignancy
Dermal Arise from single peripheral nerve Fusiform swelling of nerve 90% sporadic, 10% arise in NF1 At puberty Do not become malignant
Plexiform Arise from multiple nerve bundles "Bag of worms" (tortuous enlargement of nerves) Pathognomic of NF1 Early childhood 10% become malignant (MPNST)
Types of Schwann cells Axons Disease process
Myelinating Covers large diameter PNS axons with myelin -
Nonmyelinating Covers small diameter PNS axons with cytoplastic processes Responsible for neurofibromatosis 
 
Presentation
  • Symptoms
    • asymptomatic
    • stinging, itching, pain, disfiguration
  • Physical exam
    • reduced sensation
    • cutaneous lesions
      • can "button hole" through skin defect using finger pressure
    • signs of neurofibromatosis (2 of 7) (NIH criteria)
      • 2 or more neurofibromas, or 1 plexiform neurofibroma
      • axillary or groin freckling (Crowe's sign)
      • 6 or more coast of California cafe-au-lait spots 
        •  5mm diameter in prepubertal
        • >15mm diameter in postpubertal
      • sphenoid wing dysplasia or thinning of long bone cortex (anterolateral tibial bowing)   
      • 2 or more Lisch nodules (iris hamartomas 
        • on slit lamp
      • optic glioma  
      • 1st degree relative with NF1
    • associated with NF1
      • dystrophic kyphoscoliosis
      • rib penciling
      • intraspinal neurofibromas and dumbbell lesions  
      • dural ectasia   
      • meningiomas
Imaging
  • MRI with and without contrast    
    • findings
      • differentiate Schwannoma from neurofibroma
        • Schwannoma are found ECCENTRIC to the nerve fibers 
        • Solitary neurofibromas are found CENTRAL to the nerve fibers
    • nerve continuity sign 
      • fusiform tumor in continuity with the neurovascular bundle 
    • split fat sign 
      • fusiform tumor surrounded by a thin margin of fat because the mass within the neurovascular bundle enlarges and displaces the adjacent intramuscular fat
    • target sign 
      • lesion of high signal intensity peripherally and low signal centrally (on coronal STIR)
  • PET-CT
    • Increased uptake can help determine if malignant transformation has occurred 
Histology
  • Characteristics
    • cells
      • hypocellular 
      • predominantly fibroblasts
      • mixed Schwann cells, mast cells, lymphocytes
      • elongated, wavy nuclei
    • stroma
      • rich wire-like collagen fiber network  
      • may be myxoid
    • distorted structures resembling Pacini or Meissner corpuscles 
    • variable S100 staining
Differential
  • MPNST (malignant peripheral nerve sheath tumor or neurofibrosarcoma)
    • 5% of patients with NF, 10-25% lifetime risk
    • symptoms include painful, enlarging soft tissue mass
    • usually from plexiform neurofibroma 
      • 10% of plexiform neurofibromas transform into MPNST
    • associated with loss of expression of CDKN2A or TP53 genes in non-myelinating Schwann cells (that also have biallelic inactivation of NF1)
    • poor prognosis
      • widespread metastasis
      • high rate of local recurrence
  • Schwannoma
  • Wilms tumor
  • melanoma
  • leukemia
  • rhabdomyosarcoma
  • pheochromocytoma
Treatment
  • Nonoperative
    • observe
      • if asymptomatic
  • Operative
    • surgical excision post
      • if symptomatic
      • may require nerve grafting
 

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Questions (4)
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(OBQ13.269) A 40-year-old man presents with an 6-year history of a forearm mass and episodic, sharp forearm pain. MRI scans are seen in Figures A and B. What is the most likely diagnosis? Review Topic

QID: 4904
FIGURES:
1

Soft tissue sarcoma

11%

(364/3359)

2

Soft tissue metastasis

0%

(15/3359)

3

Hematoma

1%

(38/3359)

4

Abscess

1%

(34/3359)

5

Nerve sheath tumor

86%

(2888/3359)

ML 2

Select Answer to see Preferred Response

PREFERRED RESPONSE 5
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