Neuromuscular

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PERIPHERAL NERVE TUMORS

Large nerves
Lymphoma
Malignant Sheath
Neurofibroma
Neurofibromatosis-1
Neurofibromatosis-2
Perineurioma
Peripheral nerve tumors
Schwannoma
Tumor-like disorders



TUMOR-LIKE DISORDERS



Morton's (Plantar neuroma)

Amputation neuroma

Nerve sheath ganglion (Cyst)

Neuromuscular hammartoma (Benign Triton tumor)

Mucosal neuroma

Palisaded encapsulated neuroma

Neurothekoma

Ganglion cyst

Lipoma

PERIPHERAL NERVE TUMORS



Perineurioma: Intraneural 6

  • Nosology
  • Clinical
    • Onset age: Median 14 years; Range 0.5 to 64 years
    • Males = Females
    • Weakness
      • Frequency: > 80%
      • Causes most disability
      • Distribution
        • Usual: 1 Nerve or brachial plexus
        • Rare: Bilateral
    • Sensory: Mild
      • Loss: 65%
      • "Numbness"
      • Pain: Mild; 30%
      • Involvement less common than motor
    • Tendon reflexes: Reduced in distribution of affected nerve
    • Course
      • Slow progression (Years) or Static
      • Benign: Does not recur or metastasize
    • Tumor Locations
      • Nerves
        • Arms & Legs: Similar frequency
        • Most common: Sciatic or branches (8% to 40%)
        • Common in arms: Ulnar (17%); Median (11%); Radial (8%);
            Posterior interosseus (9%); Brachial plexus
        • Legs: Common peroneal (9%); Femoral (6%); Posterior tibial
        • Cranial: Facial; Tongue
      • Intraneural: Fusiform swelling
      • Usually single lesions: Occasionally bilateral
  • Laboratory
    • MRI
      • Segmental "fusiform" enlargement
      • T2: High intensity
      • T1: Low intensity
      • Gadolinium enhancement: Strong
    • Other imaging studies: Sonography
    • CSF: Normal protein
  • Pathology
    • Perineurioma
      • Gross structure
        • Fusiform: Segmental enlargement of affected nerve
        • Length: 2.5 to 32 cm
      • Tissue
        • Whorls: Pseudo-onion bulbs
        • Multiple layers
        • Proliferation
      • Cell morphologic features
        • Cytoplasmic processes: Thin & Elongated
        • Basal lamina: Incomplete
        • Tight junctions: Poorly formed
        • Pinocytotic vesicles
        • Well differentiated
      • Perineuriomna cell staining
        • Positive
        • Negative
          • S-100
          • Leu-7
          • Neurofilaments
      • Genetics: Somatic mutations
        • Chromosome 22q11: Homozygous deficiency
        • TRAF7 mutations
          • Location: WD40 domain
          • Frequency: 60%
          • Also occur in: Intracranial meningiomas
    • Muscle: Chronic denervation
      • Fiber type grouping
    • Differential diagnosis
      • Variant: Occurs in soft tissue
      • May mimic: Schwannomas


Localized hypertrophic mononeuropathy: Endoneurial components
  • Perineurial & Schwann cells 1
    • Clinical
      • Onset age: Mean 26 years; Range 9 to 73 years
      • Localized progressive weakness (90%)
      • Sensory loss (40%)
      • Location: Upper extremity 57%; Lower extremity 36%
      • Progression: Slow; Average 5 years to diagnosis
    • MRI (Fat suppression & gadolinium): Mass
    • Pathology
      • Whorls of perineurial cells ± Schwann cells
      • Cells
        • Stain for epithelial membrane antigen
        • Have incomplete basal lamina
  • Endoneurial fibrosis 2
    • Clinical: Progressive weakness in course of individual nerve
    • Nerves: Sciatic; Brachial plexus
    • MRI: Intrinsic abnormalities of involved nerves
    • Pathology
      • Disruption of fascicular anatomy
      • Endoneurial fibrosis
      • No involvement of perineurium or Schwann cells
Perineurioma: MRI, T2
(Sciatic nerve enlarged, Arrow)

From: C Zaidman; C Garcia


Perineurioma: Ultrasound
(Sciatic nerve enlarged, Arrow)

From: C Zaidman; C Garcia

Sciatic nerve: Ultrasound
(Opposite side, Normal)

From: C Zaidman; C Garcia


Perineurioma


Giant proximal nerve hypertrophy

Schwannoma

  • Epidemiology
    • Most common peripheral nerve tumors in adults
    • Incidence
      • 8% of intracranial tumors
      • 29% of primary spinal tumors
    • Sex
      • Overall: Male = Female
      • Intracranial lesions: Female predominance (2:1)
  • Genetics
    • Family history
      • Usually sporadic
      • Multiple (Schwannomatosis 1 (SWNTS1)) in NF2
    • NF2 mutations or 22q deletion: 77%
    • SMARCB1
      • Heterozygous: Susceptibility
      • Germline or Somntic mutations
      • Tumors: May show loss of wild type allele
      • Also associated with: Meningiomas
      • Clinical: Multiple or single tumors
    • Other related genes
      • LZTR1 , ARID1A , ARID1B , CABIN1 , DDR1 ,
        COQ6 , TAB3 , ALPK2 , CAST , TSC1 , TSC2
  • Associated disorders
  • Clinical
    • Onset age: Peak 30 to 50 years; All ages affected
    • Location
      • Solitary
      • Arise eccentrically from within nerve
      • Often at origins of spinal or cranial nerves
      • Fascicles stretched over surface of tumor
      • Cranial nerves
        • VIII: Vestibular division
        • Vagus (Recurrent laryngeal)
      • Peripheral nerves
        • Roots
          • Most at dorsal
          • Cauda equina: Intradural
        • Flexor surfaces of limbs: Near joints
        • Main nerve trunks: Peroneal; Ulnar; Sural
        • Brachial > Lumbar plexus
        • Sensory > Motor nerves
        • Digital or Cutaneous nerve: Dull pain or Tenderness
    • Symptoms
      • Most: Asymptomatic & incidentally diagnosed
      • Painful swelling
        • Shooting pain & paresthesias induced by nerve palpation
        • Spontaneous pain: Unusual; Some radicular pain
      • Sensory loss & Weakness
        • Unusual: Unless tumor located in confined space (Carpal tunnel)
      • Specific tumor locations
        • Spinal
          • Weakness
          • Bladder dysfunction
        • Cranial nerve regions
          • Hearing loss
          • Facial weakness
        • Deep tumors (e.g. mediastinal)
          • May grow large before symptoms & detection
    • Course
      • Slow growing
      • Usually benign
      • Malignant transformation
        • Not in typical tumors
        • Small risk in atypical tumors
      • Symptomatic regrowth: Rare
    • Treatment
      • Resection: Preserve nerve function & continuity
      • May be monitored if asymptomatic
  • MRI
    • T2 hyperintense
    • T1 isointense, intermediate signal
    • Gadolinium enhancement: Most sensitive; Homogeneous
    • Eccentric position to nerve
    • Cystic degeneration: Common
  • Ultrasound: Cystic lesions with sharp borders
  • Pathology
    • Cell component: Differentiated Schwann cells
    • Tumor anatomy
      • Well-circumscribed
      • Surface: Smooth
      • Shape: Elliptical or spherical
      • Extra-fasicular growth
        • Nerves of origin apparent
        • Fascicles displaced around tumor capsule
      • Location: Beyond oligodendoglial-Schwann cell junction
      • Flexor surfaces
      • May involve any nerve
    • Tissue components
      • Antoni, Type A: Highly cellular, closely packed; Verocay body
      • Antoni, Type B: Loose, myxoid
      • Degenerative changes
        • Cysts; Calcification; Hemorrhage; Hyalinization
        • Especially in large, deep tumors
      • No intratumoral axons
    • Immunoreactivity
      • S-100 protein (100%) > Leu-7
      • SOX10
      • Epithelial membrane antigen
  • Schwannoma: Atypical types
    • Ancient
      • Pathology: Cysts; Stromal edema, Xanthomatous changes; Fibrosis
      • Course: Benign
    • Psammomatous melanotic
      • Pathology: Melanin; Lamellated calcospherules
      • May occur sporadically or with Carney syndrome
      • Location: Nerve roots
      • Benign
      • Associated with cardiac myxomas
    • Cellular
      • Histology: Predominantly Antoni, Type A; May mimic malignant lesion
      • Location: Paravertebral region of retroperitoneum, pelvis, mediastinum
      • Hyperchromasia; Frequent mitoses
    • Benign Epithelioid
      • Clinical
        • Location: Extremities & Trunk (85%); Visceral (15%)
        • Metastasis: Rare
      • Histology
        • Epithelioid cells in cords or nests
        • Occasional features of degeneration (Nuclear atypia)
        • Somatic tumors
          • Dermis/subcutis
          • Encapsulated (Epithelial membrane antigen+ perineurial capsule)
        • Visceral tumors: Unencapsulated
        • Loss of SMARCB1/INI1 expression: 42%
        • Molecular: S-100 & SOX10 positive in 100%
    • Neuroblastoma-like
      • Histology: Giant rosettes; May simulate neuroblastoma
    • Plexiform
      • Conglomerate of multiple schwannomas: Occur in large nerves or plexus
      • May occur sporadically, with NF2 or with Schwannomatosis
      • Benign
      • Location: Subcutaneous tissue
      • Young adults

From: C Zaidman; C Garcia
Schwannoma: Ultrasound image



From: C Zaidman; C Garcia
Schwannoma: MRI T1 image

From: C Zaidman; C Garcia
Schwannoma: MRI T2 image

Neurofibromas

  • Genetics
    • Driven by: NF1 loss in Schwann cells
  • Number & Shape
    • Solitary in 60% to 90%
    • Neurofibromatosis: More often
      • Multiple tumors
      • Plexiform: Distal branches
      • Intraneural: Often have somatic NF1 related mutations
  • Clinical
    • Onset
      • Age: Usual 20 to 30 years; Range All
    • More often symptomatic than Schwannomas
    • Painful
      • Swelling: Palpation does not induce shooting pain
      • Radicular
    • Weakness & Sensory symptoms: With non-cutaneous nerves
    • Locations
      • Most common: Subcutaneous or Dermal
      • Some in nerve trunks: More often proximal
    • Prognosis: Malignant transformation in few
      • Solitary tumors: Rare
      • Neurofibromatosis: 4%
  • MRI
    • T2: Hyperintense periphery; Decreased central intensity (Target sign)
    • T1: Isointense with muscle; "Split fat sign" rim
    • Enhancement: Often
    • Larger than Schwannomas
    • Relation to nerve: Infiltrative
  • Pathology
    • Cell of origin: Schwann cell
    • Tumor anatomy
      • Gross: Non-encapsulated; Often plexiform
      • Intrafascicular growth: Central position in nerve
      • Shape: Fusiform or multinodular
      • Location
        • Solitary: Cutaneous nerves
        • Multiple: Non-cutaneous nerves often involved
    • Histology
      • Background
        • Disordered & Loose
        • Mucoid substance
        • Collagenous fibrils
      • Cell anatomy
        • Shape: Elongated & Wavy
        • Interlacing
        • Hyperchromatic
        • Nuclei: Spindle-shaped
      • Cell types within tumor
        • Schwann cells
        • Perineurial cells
        • Fibroblasts
        • Lymphocytes
        • Mast cells
        • Macrophages
      • Myelinated & unmyelinated axons within tumor
      • Immunoreactivity of tumor cells
        • S-100: Positive but Variable; Less than Schwannoma
        • Not Epithelial membrane antigen (EMA)
      • Compared to Schwannomas
        • Fewer Schwann cells
        • More collagen & reticulin
    • Subtypes
      • Dermal: No malignant transformation
      • Subcutaneous: No malignant transformation
      • Plexiform

From: C Zaidman; C Garcia
Neurofibroma: Ultrasound

Neurofibromatosis-1

  Neurofibromin (NF1) ; Chromosome 17q11.2; Dominant

Neurofibromatosis-2

  Chromosome 22q12.2; Dominant

Neurofibromatosis 3A, Mixed Central & Peripheral


Neurofibromatosis 4, Atypical


Malignant Peripheral Nerve Sheath Tumors (MPNST)

  • Origin
    • ? Schwann cells
    • Solitary or plexiform neurofibromas, especially irradiated
  • Frequency & Associations
    • General population (0.001%)
    • Females slightly > Males
    • Neurofibromatosis
      • Frequency in NF1: 2% to 5%
      • More common with NF-1 gene microdeletions
      • Up to 50% of MPNST
      • MPNST may arise from previoly present neurofibroma
    • Radiation
      • 10% of MPNST
      • MPNST may develop 10 to 20 years later
  • Clinical
    • Onset age: Adults; 3rd to 6th decade
    • Swelling: Spontaneous pain; Firm; Immovable;
    • Motor & sensory loss
    • Rapid change in size of neurofibroma
    • Locations
      • Sciatic nerve > Brachial & Sciatic plexus
      • Medium & Large size nerves
    • Neurofibroma related
      • New pain, weakness or neurological deficit
    • Course: Rapid progression of symptoms
    • Treatment: Wide resection or Limb amputation
    • Prognosis
      • Highly malignant; Often metastatic
      • Median survival 3 years; 5 year survival 34% to 64%
      • Worse: Large tumor (> 5 cm); NF-1; Central location
  • Tumor features
    • Size: Often large, > 5 cm
    • Margin: May be poorly defined
    • Histology
      • Necrosis
      • Mitoses
      • S-100 cells (50%)
      • Triton tumors: Contents
        • Rhabdomyosarcoma
        • Cartilage
        • Bone
        • Not mucin-secreting glands
    • Genetics: Mutations
      • Polycomb repressive complex 2 (PRC2) components
        • Somatic mutations: 70% to 92% of MPNST
        • SUZ12 somatic mutations 7
          • Present in MPNST but not in neurofibromas
        • EED
        • EZH2 : Upregulated in MPNST
        • PRC2 functions
          • Histone methyltransferase complex
            • Represses gene expression
          • Tumor suppressor
      • NF1 loss: Biallelic
      • CDKN2A : Deletions
      • Somatic mutations causing p53 deactivation
Malignant Peripheral Nerve Sheath Tumors
Features of malignancy
  Size: Large (> 5 cm)
  Enhancement patterns: Inhomogenous
    Central decreased enhancement
    Focal regions of non enhancement
  Margins: Ill defined
  Invasion of fat planes
  Perilesional edema

From: C Zaidman; C Garcia
MPNST: Ultrasound

From: C Zaidman; C Garcia
MPNST: MRI T1

From: C Zaidman; C Garcia
MPNST: MRI Contrast

From: C Zaidman; C Garcia
MPNST: MRI Contrast

From: C Zaidman; C Garcia
MPNST: MRI Contrast

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4/10/2017