Nerve Sheath Tumors

8% to 10% of all intracranial tumors

Age range: 10 to 90 years of age with peak incidence in fourth to sixth decades

Most are solitary and sporadic

4% are associated with neurofibromatosis type 2 or schwannomatosis

Account for 29% of spinal tumors; typically arise from a nerve root

No gender predilection

Account for 85% of cerebellopontine angle tumors: most arise from vestibular branch of CN VIII; referred to as “acoustic neuroma” in this location

May occasionally arise from cranial nerves (CNs V, VII, and rarely others)

Intraspinal schwannomas most typically arise from sensory nerve roots

Rare intracerebral and intramedullary spinal cord reported

Surgical resection for large tumors; radiosurgery may be appropriate for small tumors (<2.5 cm)

Rarely if ever undergo malignant transformation

Circumscribed, sometimes cystic, enhancing mass on MRI

Extension into internal auditory canal is classic for CN VIII schwannomas

Spinal tumors are extramedullary, intradural, and occasionally extend to epidural space (“dumbbell” shape)

Well-circumscribed occasionally cystic masses ranging from a few centimeters to 10 cm

Heterogeneous cut surface with yellow or hemorrhagic foci

Most are encapsulated grossly and by histology

Tumor entirely composed of differentiated Schwann cells forming two architectural patterns:

• Antoni A: closely apposed spindled tumor cells with palisading, elongated nuclei

• Antoni B: less cellular areas of loosely arranged tumor cells with indistinct processes and background microcystic change

• Verocay bodies are alternating parallel rows of nuclear palisades with areas devoid of nuclei occurring within Antoni A histology

Ancient change in schwannomas: bizarre-appearing nuclei sometimes having nuclear inclusions

Nuclear pleomorphism or an occasional mitotic figure is not an indications of malignancy

May have macrophages containing lipid

Thick-walled vessels with hyalinization and perivascular hemosiderin

Larger schwannomas may undergo degenerative necrosis and hemorrhage

Three major variants of schwannoma:

• Cellular schwannoma: hypercellular fascicular growth pattern composed mainly of Antoni A histology (Verocay bodies absent) favor paravertebral sites and cranial nerves; low mitotic activity (<4/10 HPF)

• Plexiform schwannoma: majority involve skin or subcutaneous tissues of extremities; arise in association with “schwannomatosis” syndromes

• Psammomatous/melanotic schwannoma: 50% associated with Carney complex (spotty skin pigmentation, myxomas, and endocrine overactivity); 10% undergo a malignant transformation

Strongly immunoreactive for S-100

Express Leu-7 and calretinin

Focal expression of GFAP

Consistently express collagen IV and lamin in basement membrane with the exception of melanotic variant

Electron microscopy: thin, interdigitating cell processes, basal lamina, long-spacing collagen (“Luse bodies”)

Neurofibromatosis type 2: bilateral vestibular schwannomas involving CN VIII are pathognomonic

• NF2 gene (chromosome 22q) is a tumor suppressor also implicated in sporadic tumors

• Inactivating frameshift mutations resulting in truncation of NF2 protein product, merlin, found in 60% of schwannomas

Schwannomatosis syndrome: multiple painful schwannomas in a segmental distribution in absence of other NF2 features

Psammomatous/melanotic schwannomas associated with Carney complex:

• Autosomal dominant disorder characterized by lentiginous facial pigmentation, cardiac myxoma, and endocrine disorders

• Caused by mutation of PRKAR1A gene on chromosome 17q

Cerebellopontine angle tumors: meningioma, epidermoid cyst, ependymoma

Spine: meningioma, myxopapillary ependymoma

Skin: neurofibroma

Large nerve root: malignant peripheral nerve sheath tumor