Malignant Nerve Sheath Tumor
Quick Summary Introduction References Photos		Clinical Features Histopathology Treatment Prognosis
Neurofibrosarcoma.

 

 

 

 

---

 

Quick Review for Patients

Top of This Page

 

 

 

Introduction

Note: click on underlined words for more detail or photos.

Malignant peripheral nerve sheath tumor (MPNST, malignant schwannoma, malignant neurilemoma) is now the preferred name for the spindle cell malignancy of peripheral nerve Schwann cells.  It represents approximately 10% of all soft tissue sarcomas and its diagnosis has been called "one of the most difficult and elusive diagnoses in soft tissue diseases."  It is found in at least 4% of patients with neurofibromatosis I, where its development is thought to be a multi-step, multi-gene process.  Conversely, up to half of all cases of MPNST are diagnosed in persons with neurofibromatosis I. About one in ten cases are associated with irradiation. The tumor is usually found in the lower extremities, but one-ninth of all lesions occur in the head and neck region, usually associated with the large cranial nerves, especially the trigeminal nerve. Intraosseous examples have been reported.

MPNST occurs usually in persons 20-50 years of age, but children and elderly persons may also be affected. Lesions which develop in persons with neurofibromatosis I (Figures 1 & 2) typically occur a decade or more earlier than those in non-syndrome patients. The most common head and neck area of involvement is the neck, but when this tumor occurs in the mouth it usually arises from the tongue or soft palate. There is a slight predilection toward males in sporadic cases, but within the subgroup of patients with neurofibromatosis I, 80% of lesions are found in males.

The oral lesion appears as a bosselated, usually sessile, circumscribed submucosal mass which may be associated with pain or paresthesia, or with muscle weakness and atrophy (Figures 3 & 4). Two-thirds of lesions are larger than 5 cm. at the time of diagnosis, but the tumor is considered to be a slow-growing one. At surgery, attachment to a major nerve trunk is not unusual and the surgeon may notice cystic degeneration or hemorrhage within the lesional stroma.

The MPNST resembles routine fibrosarcoma in its overall organization, but the spindled lesional cells demonstrate the wavy or comma-shaped outline and nuclear contour of Schwann cells (Figure 5). Cellular and nuclear pleomorphism may be quite pronounced and mitotic activity is usually high (Figure 6). The cytoplasm of lesional cells is usually indistinct and slightly eosinophilic. The spindle cells form into tightly packed bundles or fascicles, although these typically show greater variation than the fascicles of fibrosarcoma. Densely cellular areas are typically interspersed with hypocellular and myxoid regions in which the spindle cells are much less organized but may be focally arranged into nondescript whorled patterns (Figure 7), similar to the pacinian body-like areas found in the neurofibroma. An anaplastic MPNST does occur but is rare.

Nuclear palisading may be a striking feature (Figure 8) but is not seen in approximately half of all cases, and when present is found only in scattered, focal areas. Other distinctive but uncommon histopathologic features include: hyalinized cords surrounded by rounded lesional cells (in cross-section these resemble rosettes); perineural and intraneural spread of tumor; lesional proliferation or herniation into the lumina of small vessels. Heterotopic islands of bone, cartilage, skeletal muscle, or mucous glands are seen in more than 10% of MPNST lesions.

The MPNST may be classified into three major categories with epithelioid, mesenchymal or glandular characteristics. The epithelioid variant demonstrates plump, rounded or ovoid epithelioid cells scattered throughout the spindled lesional cells, usually in rather small numbers and in well defined clusters. These cells may have vesicular or hyperchromatic nuclei and may bear slight resemblance to the cells of the amelanotic melanoma.

Some MPNST lesions show rhabdomyoblastic differentiation leading to the common use of the diagnostic term Triton tumor. The spindle cells are interspersed with large, plump, rounded or strap cells with eosinophilic, fibrillar cytoplasm and with cross-striations in the cytoplasm. These cells may be clustered and must be distinguished from simple entrapment of striated muscles fibers.

The glandular MPNST contains areas with usually well-differentiated ductal structures lined by simple, stratified, cuboidal or columnar epithelial cells with occasional goblet cells. The lumina may contain PAS-positive, diastase-resistant mucus.

Rare MPNST cases contain multiple sarcomatous tissue types, especially osteosarcoma, chondrosarcoma and angiosarcoma. These have sometimes been indistinguishable from the malignant mesenchymoma of soft tissue.

The following antigens can be used to identify nerve sheath differentiation: S-100 protein, Leu-7, myelin basic protein.  S-100 immunoreactivity is focal and scattered in 50-90% of MPNSTs; diffuse reactivity suggests a benign neural tumor. The other two antigens show immunoreactivity in approximately half of the tumors. With electron microscopic examination, the spindled lesional cells are seen to have non-tapering, branching cytoplasmic processes extending for great distances from the cell body; these contain microtubules and neurofilaments. In well-differentiated lesions the processes are covered with basal laminae.

As previously stated, most MPNSTs resemble fibrosarcoma and may require immunohistochemistry and EM evaluation to discern useful diagnostic differences. The other sarcomas most closely resembling this tumor are leiomyosarcoma and monophasic synovial sarcoma. In the oral cavity the synovial sarcoma is so rare as to be excluded from the differential diagnosis, while the spindle cell of the leiomyosarcoma has a more distinct eosinophilic cytoplasm and a quite blunted nucleus. The cytoplasm of the latter cell is, moreover, fuchsinophilic, contains a moderate amount of PAS positive glycogen and demonstrates longitudinal striations with Masson trichrome staining.

Distinguishing the MPNST from a benign nerve sheath tumor is usually not difficult, but some neurofibromas may be quite cellular and may contain occasional pleomorphic cells. In such cases, the presence or absence of mitotic activity is usually the determining feature.

The MPNST of the oral region is treated by wide surgical excision, but local recurrence is a common occurrence and hematogenous metastasis occurs in at least half of treated cases. The tumor is resistant to radiotherapy and chemotherapy, and those occurring in neurofibromatosis I behave in a more aggressive fashion than those not associated with the syndrome. Overall, the 5-year survival for MPNST is 40-75%.

DeVore DT, Waldron CA. Malignant peripheral nerve tumors of the oral cavity: review of the literature and report of a case. Oral Surg Oral Med Oral Pathol 1961; 14:56-68.

Hutcherson RW, Jenkins HA, Canalis RF, Handler SD, Eichel BS. Neurogenic sarcoma of the head and neck. Arch Otolaryngol 1979; 105:267-270.

Tsuneyoshi M, Enjoji M. Primary malignant peripheral nerve tumors (malignant schwannomas). A clinicopathologic and electron microscopic study. Acta Pathol Jpn 1979; 29:363-375.

Ducatman BS, Scheithauer BW. Malignant peripheral nerve sheath tumor with divergent differentiation. Cancer 1984; 54:1049-1057.

Daimaru Y, Hashimoto H, Enjoji M. Malignant peripheral nerve-sheath tumor (malignant schwannoma). An immunohistochemical study of 29 cases. Am J Surg Pathol 1985; 9:434-444.

Johnson MD, Glick AD, Davis BW: Immunohistochemical evaluation of Leu-7, myelin basic protein, S-100 protein, glial fibrillary acidic protein, and LN3 immunoreactivity in nerve sheath tumors and sarcomas. Arch Pathol Lab Med 1988; 112:155-160.

Meis JM, Enzinger FM, Martz KL, et al. Malignant peripheral nerve sheath tumors (malignant schwannoma) in children. Am J Surg Pathol 1992; 16:694-707.

Hamakawa H, Kayabara H, Sumida T, Tanioka H. Mandibular malignant schwannoma with multiple spinal metastases: a case report and a review of the literature. J Oral Maxillofac Surg 1998; 56:1191-1195.