Schwannoma

Description

Schwannoma, known less commonly as neurilemmoma, is a benign peripheral nerve sheath tumour that originates from Schwann cells, which produce the myelin sheath covering peripheral nerves. These tumours can arise from any nerve covered by Schwann cells, except the optic and olfactory nerves. Schwannomas are typically solitary, well-encapsulated, and slow-growing tumours; however, they can become quite large and cause significant symptoms due to mass effect.

Pathogenesis

The exact pathogenesis of schwannomas is unclear. However, they are believed to originate from a single Schwann cell that undergoes tumourous change, hence their encapsulated nature. Schwannomas are closely associated with certain genetic conditions, specifically neurofibromatosis type 2 (NF2), which is linked to a mutation in the NF2 gene, leading to the formation of multiple schwannomas.

Subtypes

• Conventional (Antoni A/B): Biphasic pattern with Verocay bodies and myxoid areas.
• Cellular: Highly cellular, little Verocay architecture, may mimic MPNST but benign.
• Plexiform: Multinodular growth along nerve branches, seen in NF2.
• Ancient: Degenerative changes (cystic, calcified, hyalinised, nuclear atypia).
• Melanotic: Contains melanin pigment; T1 hyperintense, often psammomatous.
• Microcystic/Reticular: Network of microcysts, common in visceral locations.
• Epithelioid: Polygonal epithelioid Schwann cells; may resemble carcinoma.
• Hybrid: Features of schwannoma and neurofibroma in same lesion.

Epidemiology, Risk Factors & Associations

• Most commonly arise in adults aged 20-50 years.
• No gender predominance.
• Usually solitary and sporadic.
• Multiple schwannomas suggest:
  • Neurofibromatosis type 2 (NF2 gene mutation on chromosome 22) – characteristically bilateral vestibular schwannomas with other tumours of the nervous system
  • Schwannomatosis rare syndrome of multiple schwannaoms, without the presence of vestibular tumours that define NF2.

Clinical Features

• Symptoms are largely dependent on the location of the tumour, with most arising in the head and neck or along peripheral nerves.
• Commonly present with pain, sensory changes, or weakness in the distribution of the affected nerve.
• When associated with cranial nerve VIII (acoustic neuroma), symptoms may include hearing loss, tinnitus, and imbalance.

Complications

• Malignant transformation is rare (<1%).
• Local mass effect can lead to nerve compression and subsequent neurological deficits.

Pathological Features

Histopathology

• Macroscopic: Schwannomas are typically well-circumscribed, encapsulated, and may have a yellowish cut surface due to areas of xanthomatous change.
• Microscopic: Conventional schwannomas are characterised by two distinct histological patterns
  • Antoni A (cellular) areas – cellular and organised into cellular, intersecting fascicles, palisading nuclei alternate with nuclear-free zones (Verocay bodies)
  • Antoni B areas are less cellular and more loosely structured.

Immunohistochemistry

• S-100 positivity.

Radiological Features

General Features

• Usually seen as a well-circumscribed, encapsulated fusiform mass.
• Schwannomas are eccentric to the parent nerve, as they arise from Schwann cells which are glial cells within the myelin sheath. Hence they displace rather than infiltrate the remaining nerve fascicles and adjacent structures – a distinguishing feature from neurofibromas, which intermix with the nerve fibres.
• Commonly found in spinal and sympathetic nerve roots.
• In the extremities they usually affect nerves in the flexor surfaces of the upper and lower extremities, particularly the ulnar and peroneal nerves.
• Whilst typically solitary, if multiple, they generally occur in a cutaenous distribution, suggesting NF1.
• Intracranial schwannomas suggest NF2.
• Intratumoural hemorrhage may lead to sudden increase in size

CT

• Non-contrast: Typically appear as a well-defined, rounded mass, often iso- to slightly hyperdense compared to the muscle.
• C+ Arterial/C+ Venous: They enhance vividly on contrast due to their high vascularity.

MRI

• T1:
  • Generally iso- to hypointense compared to muscle.
  • Split-fat sign – refers to a rim of fat separating the tumour from adjacent muscles, best appreciated at the tapering margins. It helps localise the lesion to the intermuscular space and supports a benign, slow-growing peripheral nerve sheath origin
• T2:
  • Characteristically hyperintense.
  • Target sign – low signal intensity centrally (fibrocollagenous core), with a ring of higher signal intensity peripherally (myxomatous tissue)
  • Cystic degeneration may be seen in ancient subtype of schwannomas.
• T1 Gad+: Show intense, homogeneous enhancement.

US

• US appearances of schwannoma and neurofibroma overlap
• Centrally hypoechoic mass demonstrating continuity with parent nerve (most suggestive US feature)
• Posterior acoustic enhancement
• Thin echogenic peripheral capsule could reflect fibrous capsule, fibrous pseudocapsule, or compression of surrounding fat
• Target sign – Central hyperechogenicity representing fibrocollagenous component surrounded by peripheral hypoechogenicity representing myxoid component; more commonly seen in neurofibroma

Grading and Staging

No specific grading and staging system exists for Schwannomas. The tumour size and location, along with any associated symptoms, guide treatment decisions.

Reporting

• Describe centric/eccentric location of tumour to parent nerve as this affects surgical outcome

Diagnosis

Diagnosis is by imaging and may be confirmed histologically after biopsy or excision. Biopsy is often painful due to nerve involvement, so it’s usually avoided unless malignancy is suspected.

Differential Diagnosis

• Neurofibroma: A peripheral nerve sheath tumour that intermingles with the nerve fibres, unlike schwannomas which displace the nerve. The nerve fascicles may therefore visible within the tumour on MRI as multiple small ring-like structures (fascicular sign). As schwannomas do not engulf the associated nerve, surgically they can be peeled off the associated nerve at surgery. Can be associated with neurofibromatosis type 1.
• Malignant peripheral nerve sheath tumour: Usually deep lesions, involving the major nerve trunks such as the sciatic nerve, brachial plexus, and sacral plexus. Rapid interval growth, large size, irregular margins, and heterogeneous signal intensity are suggestive but non-specific signs.

Prognosis

Schwannomas generally have an excellent prognosis due to their benign nature. Surgical removal usually offers a complete cure.

Management

Surgical resection is the treatment of choice, often curative. If the tumour is not resectable or the patient is not a surgical candidate, radiosurgery or regular surveillance may be considered.