Introduction

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.

Clinical Features
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.

Pathology and Differential Diagnosis

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 PASpositive, 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 nontapering, 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.

Treatment and Prognosis

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%.

Malignant Peripheral Nerve Sheath Tumor Treatment

Malignant peripheral nerve sheath tumors (MPNST) are tumors located inside the sheath of a nerve. These tumors are a type of soft-tissue sarcoma. To treat these tumors, a patient sees an oncologist and a neurosurgeon, though a neurosurgeon may also specialize in oncology or have extensive experience in the area to ensure the best

possible treatment. Also, patients can benefit greatly from being treated by medical teams that specialize in soft-tissue sarcomas. Treatment of MPNST often involves several steps, depending on the location of the tumor, type of sarcoma, other patient circumstances and overall health. Related Searches:

1. Types
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There are three main types of treatment for MPNST. These treatments are surgical removal, radiation and chemotherapy. Doctors often use all three types in combination to create specific individual treatment plans for a patient.

Surgical Removal
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The most common treatment for malignant peripheral nerve sheath tumors is surgical resection. Resection of tumors involves the removal of the tumor and surrounding malignant tissue. The doctors analyze the edges of the area removed, and if cancerous cells remain, they excise a little more surrounding tissue. This continues until the tissues the doctors remove are clear of cancer cells, otherwise known as surgically clear borders. This surgical removal technique ensures the best possible prognosis by removing as much of the local cancer as possible.

Radiation Therapy
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Radiation is the use of specifically directed ionized radiation in a medical setting. Radiation is a common treatment for these tumors, and is often very effective at different stages. Preoperatively, radiation can reduce the size of a MPNST, making surgery easier for the doctor and therefore reducing the time spent under anesthesia. Intraoperatively, radiation helps doctors achieve clear borders without having to cut out more tissue, which is very important when the tumor is in a peripheral area such as an arm or leg. Clearing the borders without going deeper often saves the patient from an amputation. Postoperatively, radiation can destroy cancer cells that surgery couldn't remove.

Chemotherapy
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While chemotherapy is not particularly effective at treating localized MPNST, doctors often use it to treat cancer that has spread to other areas. Chemotherapy, taken either orally or intravenously, involves taking medication that kills cells.

Considerations
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MPNST can spread, and they do so, to other areas of the body. Often the lungs are the first area the cancer from these tumors metastasize to, and then the cancer can

spread to any other area of the body. MPNST are difficult tumors for doctors to treat, mainly because they are not a common type of cancer. Every treatment plan for MPNST differs based on the patient's specific circumstances and medical needs.

A malignant peripheral nerve sheath tumor (also known as "Malignant schwannoma," "Neurofibrosarcoma," and "Neurosarcoma") is a form of cancer of the connective tissue surrounding nerves. Given its origin and behavior it is classified as a sarcoma. About half the cases are diagnosed in people with neurofibromatosis; the lifetime risk for an [2] MPNST in patients with neurofibromatosis type 1 is 8-13%. MPNST with rhabdomyoblastomatous component are called Malignant triton tumors. The first-line treatment is surgical resection with wide margins. Chemotherapy (e.g. high-dose doxorubicin) and often radiotherapy are done as adjuvant and/or neoadjuvant treatment.

Causes
Soft tissue sarcomas have been linked within families, so it is hypothesized that neurofibrosarcoma may be genetic, although researchers still do not know the exact cause of the disease. Evidence supporting this hypothesis includes loss ofheterozygosity on the 17p chromosome. The p53 (a tumor suppressor gene in the normal population) genome on 17p in neurofibrosarcoma patients is mutated, increasing the probability of cancer. The normal p53 gene will regulate cell growth and inhibit any uncontrollable cell growth in the healthy population; since p53 is inactivated in neurofibrosarcoma patients, they are much more susceptible to developing tumors.
[edit]Symptoms

Symptoms may include:

Swelling in the extremities (arms or legs), also called peripheral edema; the swelling often is painless. Difficulty in moving the extremity that has the tumor, including a limp. Soreness localized to the area of the tumor or in the extremity.

[edit]Diagnosis

The most conclusive test for a patient with a potential neurofibrosarcoma is a tumor biopsy (taking a sample of cells directly from the tumor itself). MRIs, X-rays, CT scans, and bone scans can aid in locating a tumor and/or possible metastasis.
[edit]Treatment

Treatment for neurofibrosarcoma is similar to that of other cancers. Surgery is an option; the removal of the tumor along with surrounding tissue may be vital for the patients survival. For discrete, localized tumors, surgery is often followed by radiation therapy of the excised area to reduce the chance of recurrence. For patients suffering from neurofibrosarcomas in an extremity, if the tumor is vascularized (has its own blood supply) and has many nerves going through it and/or around it, amputation of the extremity may be necessary. Some surgeons argue that amputation should be the procedure of choice when possible, due to the increased chance of a better quality of life. Otherwise, surgeons may opt for a limb-saving treatment, by removing less of the surrounding tissue or part of the bone, which is replaced by a metal rod or grafts. Radiation will also be used in conjunction with surgery, especially if the limb was not amputated. Radiation is rarely used as a sole treatment. In some instances, the oncologist may choose chemotherapy drugs when treating a patient with neurofibrosarcoma, usually in conjunction with surgery. Patients taking chemotherapy must be prepared for the side effects that come with any other chemotherapy treatment, such as; hair loss, lethargy, weakness, etc.

[edit]Prognosis

Patient response to treatment will vary based on age, health, and the tolerance to medications and therapies. Also, the extent of the disease i.e. metastasis and size/location of the tumor, have an effect o n the patients recovery It is a rare tumor type, with a relatively poor prognosis.
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