Contributors: Roger E. McLendon, M.D. and David S. Enterline, M.D.
The malignant schwannoma is a malignant tumor arising from peripheral nervous tissues or showing nerve sheath differentiation. Synonyms for this entity include malignant peripheral nerve sheath tumor, neurogenic sarcoma, and neurofibrosarcoma. Because of the indefinite histologic origin of this tumor, many prefer the term Malignant Peripheral Nerve Sheath Tumor (MPNST).
The striking association of neurobibromatosis type 1 with malignant schwannomas accounts for the majority of these tumors with approximately two thirds found arising from pre-existing neurofibromas. Up to 5% of neurobibromatosis type 1 patients will develop a malignant schwannoma. An uncommon tumor, malignant schwannomas account for about 5 - 10% of malignant tumors of soft tissue. These tumors only very rarely arise from pre-existing benign schwannomas or ganglioneuromas. Sporadic variants primarily affect adults in the third to sixth decades of life, while the neurobibromatosis type 1 associated tumors arise in the third to fourth decades (around 10 years earlier).
The histology is highly variable although a fibrosarcomatous, herringbone pattern is detectable focally in the majority. The tumors are usually densely cellular and exhibit frequent mitotic figures (up to four mitotic figures per high powered field). Geographic necrosis is common. Occasionally, loose areas may interrupt the densely cellular zones while in other cases, the densely cellular zones may be perivascular. Cytologically, the elongated nuclei with tapered ends typical of benign schwannomas are often found in these tumors and helps to distinguish them from smooth muscle tumors that exhibit elongated nuclei with blunt, rounded ends.
Immunohistochemically, anti-S-100 reactivity is present but focal in the majority of cases. Anti-P53 reactivity is also commonly encountered. Proliferation indices with anti-Ki67 antibodies reveal labeling indices of 5 to 65%.
Variants of malignant schwannoma may exhibit glandular elements ("Glandular MPNST"); skeletal muscle ("Malignant Triton tumor"), or epithelioid elements ("Epithelioid MPNST")
The biological behavior of a malignant schwannoma is local growth with metastases by a hematogenous route, most commonly to the lung. The reported 5-year survival rate for patients with this tumor is as high as 50%; however it can drop to as low as 10% in patients with neurobibromatosis type 1. Involvement of the spinal canal has a particularly poor prognosis because of the difficulty of achieving total resection in this location.
The supraorbital nerve was grossly enlarged as it extended posteriorly deep into the orbit and anteriorly across the forehead. In the orbit, malignant degeneration of a preexisting neurofibroma of the orbit is associated with longstanding, well-tolerated proptosis that has recently changed, with hypesthesia in the distribution of the involved nerve, extra-ocular motility disturbances, and visual decrease. The lesions typically present in the superomedial aspect of the orbit beneath the lid and canthal skin. The lesions were palpable as cystic. At surgery, the lesions appear to be encapsulated, expanding the involved nerve. The cut surface of the tumor reveals a cream colored or gray tumor with foci of necrosis and hemorrhage that is sometimes extensive.
Systemic manifestations
Malignant peripheral nerve sheath sarcomas may arise in any location in the body, about half arise in pre-existing neurofibromas in the setting of neurobibromatosis type 1.
Physical examination will often reveal a large (2 to 6cm) irregular mass that is painful and has a history of rapid expansion. Neurological deficit in the distribution of the involved nerve is common. MRI will define the anatomy of the tumor, the presence of local invasion, and extent of metastases.
Both grossly and microscopically, these tumors may resemble either benign schwannomas or neurofibromas. The varied histologic appearance of these tumors typically invokes the panoply of soft tissue sarcomas and melanoma in the differential diagnosis. The benign cellular schwannoma may also be considered but is well encapsulated and lacks the necrosis with pseudopalisading and high mitotic activity of this high grade sarcoma (Woodruff et al., 1981; Fletcher et al., 1987).
Treatment
Care must be taken to distinguish this tumor from the benign schwannoma in that complete surgical excision with wide margins provides the best chance of long term survival.
The maligant schwannoma is a schwannoma that has undergone malignant transformation.h is typically stretched over the tumor without involvement of the axons. It is composed of well-differentiated spindle shaped Schwann cells with moderately abundant, fibrillar, eosinophilic cytoplasm. The schwannoma may be associated with both neurofibromatosis type I (such as spinal cord schwannomas) and neurofibromatosis type II (bilateral schwannomas of the acoustic nerves as well as schwannomas along the spinal nerve roots). The tumor is usually light tan in color, but may be hemorrhagic reddish-brown in larger tumors. The clinical symptoms relate to the location of the tumor.
The light micrscopic hallmarks of schwannomas are Antoni type A tissue, Antoni type B tissue and the Verocay body. Mitotic activity is unusual. Acoustic nerve schwannomas typically exhibit abundant Antoni type B tissue T, but lack well-formed Verocay bodies. Mild nuclear pleomorphism may be evident (ancient change) and it is generally associated with more abundant fibrous stroma, focal calcification, microcystic and mucinous change, and xanthomatous change of the tumor cells.These areas may also contain hyalinized and thickened vessels, hemosiderin, acute hemorrhage, and mononuclear inflammatory infiltrates.
Some schwannomas exhibit a high cellular density, nuclear atypia and rare mitoses. The high cellular density is at least partially related to a mononuclear inflammatory infiltrate in the tumor. These cellular schwannomas often raise the issue of malignancy. The vast majority of them arise intraspinally or intracranially. Of these tumors, mitotic index most closely correlated with recurrence in incompletely excised tumors. Antoni Type B tissue is scant but present. Necrosis is rare and typically small. Pseudopalisading of tumor cells around necrosis should raise the diagnosis of malignancy. Mitotic activity falls in the range of 2 to 4 per ten fields in these cases. In contrast to some reports, the cellular schwannoma is benign.
Schwannomas may involve the infra-orbital nerve. The tumors typically present as slowly enlarging tumors resulting in proptosis, extraocular muscle dysfunction, and occasionally pain. Orbital enlargement may be seen by radiographic studies. Schwannomas arising near the optic nerve may produce visual disturbances.
Schwannomas may occur anywhere in the body along a nerve twig including intraosseously, within abdominal viscera, intracranially, and intramuscularly. They typically follow a benign course and produce symptoms via mass effect and, rarely, pain.