Schwannoma

Synonyms: Neurilemoma [Soft Tissues], Neurinoma [Soft Tissues]

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Definition

Benign, encapsulated tumors of differentiated Schwann's cells, usually localized in peripheral nerves.

Clinical Features

Almost always solitary
Location:
- most commonly:
  - flexor surfaces of extremities
  - neck
  - mediastinum
  - retroperitoneum
  - posterior spinal roots
  - cerebellopontine angle1

Pathogenesis

Generally agreed that originates from Schwann's cells2

Gross Pathology

Encapsulated
Nerve of origin:
- often demonstrated in periphery flattened along capsule but not penetrating substance of tumor (Fig. 1
  Fig. 1: Schematic drawing emphasizing the main differences between the three major types of peripheral nerve tumors. Note diameter of nerve involved and behavior of neurites (thin black lines) in relation to neoplasm.
  )
Often contain cystic areas if large (Figs 2 and 3
Fig. 2: Gross appearance of schwannoma.
Fig. 3: Gross appearance of schwannoma. The tumor has undergone marked secondary cystic changes.
)

Histopathology

Usually two different patterns:
- Antoni A areas:
  - almost entirety of small tumors
  - quite cellular
  - composed of spindle cells:
    - often:
      - palisading (Fig. 4
        Fig. 4: Schwannoma with a suggestion of nuclear palisading and hyaline thickening of vessel walls.
        ) or
      - organoid arrangement (Verocay bodies)
- Antoni B areas:
  - tumor cells separated by abundant edematous fluid, which may form cystic spaces
  - occasionally isolated cells with bizarre hyperchromatic nuclei3 (Fig. 5
    Fig. 5: Large hyperchromatic nuclei in schwannoma. This is not necessarily an indication of malignant change.
    ):
    - common in ‘ancient schwannomas’
    - no particular significance4
Mitoses:
- usually absent or scanty
Blood vessels:
- can be prominent and simulate vascular neoplasm (Fig. 6
  Fig. 6: Schwannoma showing large vascular spaces that may lead to confusion with a vascular neoplasm. Hemosiderin-laden macrophages are also present as evidence of previous hemorrhage.
  )
- ultrastructurally fenestrated type5
- commonly:
  - thrombosis
  - hyaline thickening of adventitia
Sometimes large nodular masses of collagen with radiating edges:
- sometimes descriptively designated as:
  - ‘amianthoid’ fibers, or
  - collagenous spherules
- most soft tissue tumors with these formations are derived from peripheral nerve sheath6–8
Axons not present except in portion of capsule where nerve attached
Sometimes collections of foamy macrophages, especially in larger neoplasms
More unusual:
- clusters of granular cell similar to those in granular cell tumors 9
May be:
- epithelioid areas:
  - much less common than in MPNST10,11
  - when predominate has been referred to as benign epithelioid schwannoma12
- glandular component (benign glandular schwannoma):13,14
  - rule out sweat gland entrapment before making diagnosis
Rarely:
- plexiform areas:
  - may cause mistaken diagnosis of neurofibroma 15,16
- melanin pigment:17
  - when prominent and psammoma body formation consider psammomatous melanotic schwannoma18
Exceptionally:
- typical schwannomas or those with epithelioid features contain foci of small round hyperchromatic Schwann's cells with scanty cytoplasm:
  - sometimes forming rosettes and simulating neuroblastoma19,20
Ultrastructurally (Fig. 7
Fig. 7: Electron microscopic appearance of schwannoma of retroperitoneum. Elongated cells with processes are partially covered by basal lamina. Cells contain lipid of varied density.
) tumor cells have:
- continuous basal lamina
- numerous extremely thin cytoplasmic processes
- aggregates of intracytoplasmic microfibrils
- peculiar intracytoplasmic lamellar bodies
- extracellular long-spacing collagen:21–24
  - not specific for peripheral nerve cell tumors 25

Special Stains and Immunohistochemistry

Tumor cells immunoreactive for:
- S-100 protein (Fig. 8
  Fig. 8: S-100 protein immunoreactivity in schwannoma.
  )
- calcineurin
- basal lamina components such as:
  - laminin
  - type IV collagen
  - merosin
- vimentin
- nerve growth factor receptor
- lipocortin-1
- sometimes:
  - glial fibrillary acidic protein
  - KP-l (CD68)22,26–38
- disputed whether positive for myelin markers such as:
  - P2 protein 39
- do not express:
  - keratin
  - desmoplakin
  - neurofilaments
  - desmin28

Diagnosis

Variants

Cellular Schwannoma

Highly cellular (Figs 9 and 10
Fig. 9: Cellular schwannoma. Gross appearance. The tumor has a homogeneous hypercellular quality.
Fig. 10: Cellular schwannoma. Microscopic appearance. The tumor has a homogeneous hypercellular quality.
)
Exclusively composed of Antoni A areas
Lack Verocay bodies40,41
May be:
- nuclear atypia
- mitotic activity
- focal necrosis
Usually in:
- mediastinum 42,43
Differential diagnosis with low-grade MPNST difficult and controversial

Psammomatous Melanotic Schwannoma

Component of Carney's syndrome 18
Most arise from spinal nerve roots36,44
Characterized microscopically by:
- melanin pigmentation (Fig. 11
  Fig. 11: Melanocytic psammomatous schwannoma in a patient with Carney's syndrome.
  )
- psammoma bodies
Low-grade malignancy:
- tendency for local recurrence
- occasional metastasis18

Differential Diagnosis

Select up to 2 differential diagnoses to compare with Schwannoma

Palisading of nuclei also in:
- leiomyoma
- leiomyosarcoma
- GIST
- calcifying aponeurotic fibroma
- non-neoplastic smooth muscle (most commonly appendiceal wall)

Management

Attempt to preserve nerve if clinically significant (e.g. facial nerve or vagus nerve)

Prognosis

Benign
Rarely recurs locally
Malignant transformation exceptionally rare:45,46
- usually malignant component has epithelioid morphology

References

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3 Lin BT, Weiss LM, Medeiros LJ. Neurofibroma and cellular neurofibroma with atypia: a report of 14 tumors. Am J Surg Pathol. 1997;21:1443–1449.

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34 Leivo I, Engvall E, Laurila P, Miettinen M. Distribution of merosin, a laminin-related tissue-specific basement membrane protein, in human Schwann cell neoplasms. Lab Invest. 1989;61:426–432.

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36 Mennemeyer RP, Hammar SP, Tytus JS, Hallman KO, Raisis JE, Bockus D. Melanotic schwannoma. Clinical and ultrastructural studies of three cases with evidence of intracellular melanin synthesis. Am J Surg Pathol. 1979;3:3–10.

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39 Clark HB, Minesky JJ, Agrawal D, Agrawal HC. Myelin basic protein and P2 protein are not immunohistochemical markers for Schwann cell neoplasms. A comparative study using antisera to S-100, P2, and myelin basic proteins. Am J Pathol. 1985;121:96–101.

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Last updated: 21 Feb 2006