Dx: distinctive features suggesting peripheral nerve sheath tumor:
- Location in region of a major nerve
- Depiction of nerve entering / exiting mass
- Presence of split fat sign, fascicular sign, target sign
MR:
- “split-fat” sign = lesion surrounded by a rim of fat ← displacement of fat surrounding neurovascular bundle suggesting a tumor origin in intermuscular space
- “fascicular” sign = multiple small ringlike structures with peripherally higher SI on T2WI ← fascicular bundles within nerves
- “target” sign= fibrocollagenous tissue centrally and myxomatous tissue peripherally:
- tumor periphery of high SI ← myxoid degeneration
- center of tumor of low SI ← fibrocollagenous tissue of condensed Schwann cells
Angio:
- displacement of major vascular structures
- corkscrew-type vessels at upper / lower pole of tumor (= hypertrophy of nutrient nerve vasculature)
Benign Peripheral Nerve Sheath Tumor
= (BENIGN PNST) = BENIGN TUMOR OF NERVE SHEATH = NEURINOMA
Frequency: 10% of benign soft-tissue tumors
Schwannoma = Neurilemmoma
[neuron, Greek = nerve, sinew; eilema, Greek = covering, coil]
= usually solitary well-encapsulated slow-growing benign proliferation of Schwann cells in a collagenous matrix → eccentric displacement of nerve fibers
- Schwann, Theodor (1810–1882), German physiologist at Belgian Universities Löwen/Leuven/Louvain and Lüttich/Liège cell = cell that surrounds cranial, spinal, and peripheral nerves producing myelin sheath around axons thus providing mechanical protection and serving as a tract for nerve regeneration
- NOTE that myelin sheaths within brain substance are made by oligodendrocytes!
- [Theodor Schwann (1810–1882), German physiologist at Belgian Universities Löwen/Leuven/Louvain and Lüttich/Liège]
◊Nerve root NOT incorporated
Prevalence: 5% of all benign soft-tissue tumors
Age: 40–60 years; M=F
Uncommonly associated with: neurofibromatosis type 1
Path:
- fusiform mass entering + exiting the nerve
- mass exophytic / eccentric to nerve of origin
- surrounded by a true capsule of epineurium
- nerve flattened against periphery of tumor
Histo: positive for S-100 protein + vimentin + CD56
- cellular component (Antoni type A tissue):
more organized area composed of densely packed cellular spindle cells with carrot-shaped or wavy nuclei arranged in short cordlike bundles / interlacing fascicles forming Verocay bodies (= palisading arrangements of elongated cells)
[Nils RE Antoni (1887-1968), professor of neurology at Karolinska Institutet in Stockholm, Sweden]
Location: posterior mediastinum, retroperitoneum, 25% of extremity lesions- hypointense on T2WI
- smaller lesion with uptake of contrast material
- myxoid component (Antoni type B tissue):
less organized loosely arranged stellate cells in a mucoid stroma (= hypocellular myxoid tissue with high water content)- larger lesion hyperintense on T2WI
- ancient / cystic schwannoma (see below)
- Antoni type A & B often coexist in a single tumor!
- painless, fairly mobile mass
- ± motor and sensory nerve disturbance
Location: in typical peripheral nerve distribution (94%)
- intracranial: mostly from sensory nerves
- Vestibulocochlear (CN VIII) nerve (most common) >trigeminal (V) cranial nerve (2nd most common) >VII
- Usually sporadic tumor, but 5–20% of patients with solitary intracranial schwannomas have NF2!
- extracranial:
- Orbit (rare): branches of trigeminal (V) nerve (most common) >oculomotor >trochlear >abducens >parasympathetic >sympathetic fibers >ciliary ganglia
- Neck, flexor surfaces of upper + lower extremities
Site: ulnar n., peroneal n.- Usually solitary, but in 5% associated with neurofibromatosis type 1 (= >2 schwannomas / one plexiform neurofibroma)
- Spine
Location: spinal and sympathetic nerve roots; most common in lower thoracic and lumbar spine >presacral
Site: intradural (70–75%), extradural (15%), both intra- and extradural (15%), intramedullary (<1%) - Posterior mediastinum + retroperitoneum (commonly paravertebral, adjacent to kidneys)
Frequency: 6% of retroperitoneal neoplasms - Abdominal wall
Size: 0.1–2.5 cm at time of surgery
Plain film:
- fusiform mass delineated by surrounding fat
- soft-tissue and osseous overgrowth
- bone involvement + mineralization (osteoid / chondroid / amorphous) only in larger lesions
US:
- hypoechoic well-circumscribed mass ± cystic spaces
CT:
- solitary fusiform well-encapsulated round tumor:
- entering + exiting nerve (intradural / extradural)
- dumbbell shape with extension into enlarged neural foramen (intra- and extradural)
- low attenuation (as low as 5–25 HU) due to
- high lipid content of myelin from Schwann cells
- entrapped fat
- endoneural myxoid tissue with high water content (Antoni B areas)
- well-defined hyperdense margins
- marked uniform enhancement (most helpful for intradural lesions)
- slow growth
- homo- / heterogeneous (33%) enhancement: homogeneous (heterogeneous) if small (large)
- muscle atrophy with striated increased fat content (in 23%)
- punctate / mottled / curvilinear calcifications
MR:
- well-delineated mass of hypo– to isointense signal relative to skeletal muscle on T1WI
- moderate to markedly increased slightly heterogeneous signal intensity on T2WI:
- T2 hypointense foci centrally ← dense cellularity / collagen / hemorrhage
- markedly T2 hyperintense focal areas ← zones of fluid signal = cystic degeneration
- frequently low-signal-intensity rim ← capsule
- peritumoral edema in 33%
Cx: malignant transformation (rare)
Rx: excision (affected nerve usually separable from neoplasm after incision of epineurium)
DDx: may appear similar to meningioma
Ancient / Cystic Schwannoma
= rare variant of schwannoma characterized by marked degenerative changes (old hemorrhage, calcification, cystic change) + decreased cellularity
Age: elderly
Histo: significantly decreased Antoni type A (hypercellular) area with Antoni type B areas occupying majority of tumor
Location: head & neck (orbit, intraventricular, olfactory groove, cavernous sinus), mediastinum, retroperitoneum, pelvis
- heterogeneously enhancing mass with cystic areas ← myxoid + hemorrhagic change
- fluid-fluid levels ← hemorrhage
- ± calcifications / ossification
DDx: serous / mucinous cystadenocarcinoma, abscess, necrotic metastatic lymphadenopathy, arachnoid cyst, dermoid cyst
Ganglioneuroma
Origin: ganglion cell
Mean age: 7 years; M<F
Histo: mature gangliocytes and stroma
- Neuroblastoma + ganglioneuroblastoma may mature into ganglioneuroma!
Location: sympathetic ganglia (commonly in mediastinum and retroperitoneum)
- rarely symptoms of catecholamine excess (= vanillylmandelic acid / homovanillic acid)
Average size: 8 cm
Histo: stroma composed of Schwann cells + variable amounts of mature ganglion cells; stains with neuron-specific enolase, neurofilament protein, synaptophysin
US:
- well-defined homogeneously hypoechoic mass
- ± punctate echogenic foci ← calcifications
CT:
- speckled / coarse calcifications within solid homogeneously hypoattenuating mass
- mild to moderate homogeneous / heterogeneous enhancement
MR:
- low T1 SI + heterogeneous high T2 signal intensity
- heterogeneous progressive enhancement
NUC:
- ± metaiodobenzylguanidine (MIBG) uptake
Rx: complete surgical resection
Neurofibroma
= benign slow-growing peripheral nerve sheath tumor → fusiform enlargement of nerve by separating nerve fibers
Prevalence: 5% of all benign soft-tissue tumors
Path:
- round / ovoid mass arising from nerve fascicle
- centrally located mass intrinsic to host nerve
- often infiltrative + rarely encapsulated
- inseparable from parent nerve with tendency to insinuate between tissue planes
Histo: swirls of neuronal elements containing fibroblasts, Schwann cells, nerve fibers; spindle-shaped cells arranged in ribbons and cords among a background of loose myxoid stroma; tumor expresses S100
Typical Demographic and Radiologic Features of Nerve Sheath Tumors
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Types: localized (90%), diffuse, plexiform
Age: 20–30 years; M÷F = 1÷1
In 10% associated with: neurofibromatosis type 1 (HALLMARK lesion of NF1)
- Neurofibroma is the hallmark lesion of NF1!
- Schwannoma is more characteristic of NF2!
Location: skin, soft tissues, viscera; any level, but particularly cervical
- peripheral nerves
- nonencapsulated well-circumscribed fusiform mass of peripheral nerves
- intradural extramedullary mass
- The spinal neurofibroma is rarely sporadic and usually a sign of type 1 neurofibromatosis!
- well-defined mass of dumbbell configuration (= intradural + extradural component extending through neural foramen)
- widening of intervertebral foramen + erosion of pedicles
- scalloping of vertebral bodies
US:
- nonspecific solid round / oval mass
- well-defined homogeneously hypoechoic lesion
- may demonstrate posterior acoustic enhancement
- “target” appearance = more hypoechoic periphery (= homogeneous myxoid material) and hyperechoic central zone (= fibrocollagenous core)
CT:
- well-defined round / oval homogeneously hypodense (CHARACTERISTIC) mass of 20–25 HU (= mucinous matrix + lipid-rich Schwann cells + adipocytes + entrapment of adjacent fat + cystic degeneration)
- fusiform shape ← entering + exiting nerve = best imaging feature
CECT:
- typically homogeneous enhancement (30–50 HU)
- occasionally targetlike enhancement
MR:
- homogeneous mass hypo- to isointense to cord / muscle on T1WI
- T2 hyperintense with some heterogeneity
- “target sign” = central T2-hypointense area (← central core of collagenous + fibrillary tissue) surrounded by high peripheral T2 signal (← fat and myxoid matrix / cystic degeneration, hemorrhage, calcifications)
- “whorled” appearance with T2 hypointense curvilinear areas ←bundles of collagen and Schwann cells
CEMR:
- ringlike enhancement of areas of low T2 signal (= myxoid stroma / complex fascicular arrangement)
- ± muscular atrophy
Cx: malignant transformation (7–13% lifetime risk) → rapid growth, necrosis, hemorrhage, calcification, loss of “target sign”, invasion of adjacent structures associated with edema
Rx: surgical resection with sacrifice of nerve (tumor not separable from normal nerve)
DDx: conjoined nerve root sleeve
Amputation neuroma (extremely rare)
= TRAUMATIC NEUROMA
= nonneoplastic proliferation of the proximal end of a severed / partially transected injured nerve
Histo: nonencapsulated tangled multidirectional regenerating axonal masses + Schwann cells + endo- and perineural cells in dense collagenous matrix with surrounding fibroblasts
Types:
- spindle neuroma = internal focal fusiform swelling
Cause: chronic friction / irritation of nondisrupted injured but intact nerve trunk - lateral / terminal neuroma
Cause: severe trauma with partial avulsion / disruption / total transection of nerve
Time of onset: 1–12 months after injury
- history of prior surgery
- Tinel sign = palpation / tapping on lesion reproduces pain
Location: lower extremity (after amputation), head and neck (after tooth extraction), radial nerve, brachial plexus
- fusiform mass / focal enlargement with entering and exiting nerve (spindle type)
- bulbous mass in continuity with normal nerve proximally (lateral / terminal type)
MR:
- isointense to muscle on T1WI
- heterogeneous intermediate to high SI on T2WI
- “fascicular” sign = heterogeneous ringlike T2 pattern
Rx: acupuncture, cortisone injection, transcutaneous / direct nerve stimulation, physical therapy, surgical resection
Localized Solitary Neurofibroma (90%)
Prevalence: 90% of all neurofibromas
Path: fusiform tumor, often remaining within epineurium as a true capsule
Histo: interlacing fascicles of wavy elongated cells containing abundant amounts of collagen
- painless fusiform mass
Location: affecting primarily superficial cutaneous nerves, occasionally deep-seated larger nerves
- mostly solitary slow-growing lesion <5 cm in size
- Solitary lesion associated with NF1 in ~ 12%!
US:
- homo- or heterogeneous hypoechoic mass
MR:
- “string” sign = visualization of entering + exiting nerve roots at both ends of vertically oriented fusiform mass
- characteristically low signal intensity on T1WI
- heterogeneously high on T2WI:
- high SI on T2WI ← areas of cystic degeneration / myxoid matrix
- areas of low T2 signal show enhancement ← collagen + fibrous tissue
DDx: schwannoma (encapsulated, difficult DDx)
- Orbit
Location: superior extraconal orbit- hypoglobus = downward displacement of globe
Diffuse Neurofibroma
Age: children + young adults
Path: poorly defined lesion within subcutaneous fat, infiltrating along connective tissue septa, inseparable from normal nerve tissue
Histo: very uniform prominent fibrillary collagen
Location: most frequently in subcutaneous tissues of head + neck
- plaquelike elevation of skin with thickening of entire subcutis
- Isolated lesion (in 90%) unassociated with NF1!
- always indistinct infiltrative margins ← subcutaneous spread along connective tissue septa
- hypointense on T2WI
Plexiform Neurofibroma
= involvement of a long segment of nerve + branches extending into adjacent muscle, fat, subcutaneous tissue
Histo: heterogeneous mixture of Schwann cells, perineural cells and fibroblasts
Age: earlier age than other neurofibromas
Location: nerve plexus / multiple fascicles in a medium- to large-sized nerve like lumbosacral plexus; usually bilateral + symmetric
- In combination with multiple localized neurofibromas PATHOGNOMONIC of neurofibromatosis type 1
- reticulated linear branching pattern within subcutaneous tissue; often large disfiguring mass
- serpentine “bag of worms” appearance = tortuous tangles / fusiform enlargement of a branching peripheral nerve
- ropelike mass involving nonbranching nerve
- infiltrative mass without respect for fascial boundaries (= transspatial involvement)
- heterogeneous uptake of contrast material
US:
- homo- or heterogeneously hypoechoic well-defined masses
CT:
- iso- or hypoattenuating infiltrative mass ← lipid-rich Schwann cells + adipocytes + myxoid change
- “targetlike” with benign neurogenic tumor (in 52%)
- hypovascular / intensely enhancing soft-tissue mass
MR:
- innumerable ringlike structures corresponding to cross sectioning of ropelike masses
- T1 + T2 prolongation:
- heterogeneous intensity on T1WI
- marked T2-hyperintensity with multiple linear hypointense areas
- diffuse intense contrast enhancement
- typically “targetlike” pattern on T2WI:
- peripheral high SI (← myxoid stroma)
- central low SI (← fibrous-collagenous tissue)
- Orbit (1st division of CN V in orbital apex):
Path: tumor may cross tissue planes + involve large portions of face- enlargement of affected orbit + neural foramina and erosion of orbital walls + skull base (esp. sphenoid)
Cx: potential for malignant transformation to malignant peripheral nerve sheath tumor (5%)
DDx: lymphatic malformation (fluid-fluid levels)
Malignant Peripheral Nerve Sheath Tumor
= (MPNST) MALIGNANT TUMOR OF NERVE SHEATH = NEUROFIBROSARCOMA = MALIGNANT SCHWANNOMA = NEUROGENIC (SPINDLE CELL) SARCOMA
Prevalence: 5–6–10% of all soft-tissue sarcomas
Lifetime risk in NF1: 4–5%
Age: 20–50 years (mean, 26 years); M÷F = 1÷1
Associated with: neurofibromatosis type 1 (in 10–50–70%), radiation therapy (in 11% of all malignant PNSTs after a latent period of 10–20 years)
Path: fusiform mass with areas of necrosis (in 60%)
Histo: tumor cells arranged in fascicles in a herring-bone pattern resembling fibrosarcoma; additional heterotopic foci with mature cartilage and bone, rhabdomyosarcoma elements, glandular and epithelial components (in 10–15%)
- progressive enlargement
- pain, motor weakness, sensory deficits in extremity
- clinically silent tumors in abdomen + retroperitoneum
Location: major nerve trunks (commonly in proximal extremities + paraspinal region of torso (sciatic n., sacral plexus, brachial plexus); head & neck
Size: frequently >5 cm in diameter
Metastases: lung, bone, pleura, retroperitoneum (60%); regional lymph nodes (9%)
- fusiform mass with entering + exiting nerve typically larger than benign PNST
- frequently indistinct irregular + infiltrative margins = aggressive biology
- sudden increase in size of a previously stable neurofibroma
- heterogeneous tumor with heterogeneous enhancement ← areas of hemorrhage + necrosis
- invasion of adjacent organs → destruction of adjacent vertebrae / pelvic bones (NO difference to benign PNST)
NUC:
- 67Ga-citrate uptake in majority of MPNST (DDx: benign tumors show no uptake)
N.B.: only helpful in 67Ga-positive tumors (← false negative rate unknown for MPNST)
Rx: resection + adjuvant chemo- and radiation therapy with local recurrence in 40%
Prognosis: highly aggressive tumor with a 44% 5-year survival rate