Malignant peripheral nerve sheath tumor (ORPHA:3148)
Malignant peripheral nerve sheath tumor (MPNST) is a rare and often aggressive soft tissue sarcoma occurring in a wide range of anatomical sites.
Epidemiology
Exact prevalence and incidence are unknown. Incidence of MPNST in the general population has been reported to be 1/100,000. MPNSTs account for about 5 to 10% of all soft tissue sarcomas. The sex ratio is about equal. Incidence among neurofibromatosis type 1 patients (NF1; see this term) is reported to be approximately 5 to 10%.
Clinical description
The age of occurrence is highly variable but most cases are reported in adults (typically between 20 and 50 years of age). In most cases, tumors arise in major nerve trunks such as the sciatic nerve or in the brachial plexus and sacral plexus. They are highly variable in appearance and commonly present as a rapidly enlarging palpable mass that is sometimes painful, with associated neurologic deficits such as radicular pain, paresthesia, and motor weakness. Tumors are fusiform to globular in shape, usually well circumscribed, and can be white to yellow and soft or firm. They occur most commonly in the trunk, head, neck and proximal extremities. Very rare anatomical sites include the brain, breast, posterior mediastinum, bladder, adrenal gland and skin. Tumors are often aggressive and high-grade, with the tendency to recur or to metastasize. MPNSTs can occur sporadically or in patients with NF1. They occur either de novo or from a preexisting neurofibroma or rarely from a schwannoma.
Etiology
The etiology is unknown. Identified gene alterations include loss of the NF1 (17q11.2) and TP53 tumor suppressor gene (17p13.1). About 10% of tumors are associated with prior therapeutic or environmental radiation exposure.
Diagnostic methods
Histopathological examination is needed for definitive diagnosis. Biopsy usually reveals MPNST to be an infiltrative neoplasm with a varied range of cell morphologies (spindle, rounded or fusiform cells), with cellular fascicles which alternate with myxoid regions (marbled pattern). Diagnosis may be challenging because there are no specific immunohistochemical or molecular markers. Radiological imaging is used to determine the site and extension of the tumor.
Differential diagnosis
Other malignant neoplasms to include in the differential diagnosis include synovial sarcoma, fibrosarcoma, undifferentiated pleomorphic sarcoma, angiosarcoma (see these terms), melanoma, and myoepithelial tumors.
Management and treatment
Total surgical resection is the mainstay of treatment. If removal is not possible, excision combined with high-dose radiation therapy may be used. Local Radiotherapy may be beneficial, but appears to have little effect on long-term survival. Chemotherapy is generally not effective.
Prognosis
Prognosis is generally poor and depends on the size of the tumor and success of treatment. A less favorable prognosis is associated with large tumors, NF1-associated cases, and truncal localization. The recurrence rate is reported to be as high as 40% and approximately two thirds of cases metastasize (lungs and bone). Five-year survival rate is reported to be 26% to 60%, and 10-year survival to be around 45%.

                            Last update: 
                            August 2014


                            - Expert reviewer(s): 
                            Dr Khin THWAY