Malignant peripheral nerve sheath tumor overview

# Overview
Malignant peripheral nerve sheath tumor (MPNST) is a form of cancer of the connective tissue surrounding nerves. On gross pathology, a large firm mass with necrosis and hemorrhage is the characteristic finding of malignant peripheral nerve sheath tumor. On microscopic histopathological analysis, spindle cells, nuclear atypia, mitoses, and herring bone pattern are characteristic findings of malignant peripheral nerve sheath tumor. Neurofibromatosis type I (NF1) gene is involved in the pathogenesis of malignant peripheral nerve sheath tumor. Malignant peripheral nerve sheath tumor must be differentiated from neurofibroma and schwannoma. The incidence of malignant peripheral nerve sheath tumor is approximately 0.1 per 100,000 individuals worldwide. The incidence of malignant peripheral nerve sheath tumor increases with age. Malignant peripheral nerve sheath tumor affects men and women equally. Common risk factors in the development of malignant peripheral nerve sheath tumor are pre-existing plexiform neurofibromas, pre-existing perineuriomas, radiation therapy, and neurofibromatosis type 1. Symptoms of malignant peripheral nerve sheath tumor include peripheral edema, difficulty in moving the extremity, pain, and numbness. MRI may be diagnostic of malignant peripheral nerve sheath tumor. Findings on MRI suggestive of malignant peripheral nerve sheath tumor include isointense on T1 weighted image and low signal on T2 weighted image. The predominant therapy for malignant peripheral nerve sheath tumor is surgical resection. Adjunctive chemotherapy and radiation therapy may be required. Common complication of malignant peripheral nerve sheath tumor is metastasis. Prognosis is generally poor.

# Classification
There is no classification system established for malignant peripheral nerve sheath tumor.

# Pathophysiology
On gross pathology, a large firm mass with necrosis and hemorrhage is the characteristic finding of malignant peripheral nerve sheath tumor. On microscopic histopathological analysis, spindle cells, nuclear atypia, mitoses, and herring bone pattern are characteristic findings of malignant peripheral nerve sheath tumor. Neurofibromatosis type I (NF1) gene is involved in the pathogenesis of malignant peripheral nerve sheath tumor.

# Causes
Malignant peripheral nerve sheath tumor may be caused by a mutation on neurofibromatosis type I gene.

# Differential Diagnosis
Malignant peripheral nerve sheath tumor must be differentiated from neurofibroma and schwannoma.

# Epidemiology and Demographics
Malignant peripheral nerve sheath tumors comprise 2% of all sarcomas whichare a small fraction of a group of cancers that affect 5 people per million per year. The incidence of malignant peripheral nerve sheath tumor is approximately 0.1 per 100,000 individuals worldwide. The incidence of malignant peripheral nerve sheath tumor increases with age. Malignant peripheral nerve sheath tumor affects men and women equally.

# Risk Factors
Common risk factors in the development of malignant peripheral nerve sheath tumor are pre-existing plexiform neurofibromas, pre-existing perineuriomas, radiation therapy, and neurofibromatosis type 1.

# Screening
According to the the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for Malignant peripheral nerve sheath tumor.

# Complication and prognosis
In general Malignant peripheral nerve sheath tumor is known to have high metastatic potential and poor prognosis. long-term outcomes vary widely across multiple series, with 5-year survival ranging between 15% and 50%. Large tumor size at presentation (typically >5 cm) has been the most consistently determined adverse prognostic factor. Other reported factors include tumor grade, truncal location, surgical margin status, local recurrence, and heterologous rhabdomyoblastic differentiation. The true prognostic impact of NF1 syndrome in MPNST remains somewhat in flux. Several large series report significantly worse outcomes for MPNST arising in the setting of NF1 compared with sporadic disease, with inferior responses to cytotoxic chemotherapy and 5-year survivals that are up to 50% worse.

# Diagnosis

## Staging
There is no established system for the staging of malignant peripheral nerve sheath tumor.

## Symptoms
Symptoms of malignant peripheral nerve sheath tumor include peripheral edema, difficulty in moving the extremity, pain, and numbness.

## Physical Examination
Common physical examination findings of malignant peripheral nerve sheath tumor include edema, paresthesia, and weakness.

## Laboratory Findings
There are no laboratory findings associated with malignant peripheral nerve sheath tumor.

## X Ray
There are no X-ray findings associated with malignant peripheral nerve sheath tumor.

## CT
CT scan may be diagnostic of malignant peripheral nerve sheath tumor. Finding on CT scan suggestive of malignant peripheral nerve sheath tumor is a rapid growth mass with irrefular border.

## MRI
MRI may be diagnostic of malignant peripheral nerve sheath tumor. Findings on MRI suggestive of malignant peripheral nerve sheath tumor include isointense on T1 weighted image and low signal on T2 weighted image.

## Ultrasound
There are no ultrasound findings associated with malignant peripheral nerve sheath tumor.

## Other Imaging Findings
Scintigraphy may be diagnostic of malignant peripheral nerve sheath tumor. Finding on Gallium67 scintigraphy suggestive of malignant peripheral nerve sheath tumor is higher uptake.

## Other Diagnostic Studies
There are no other diagnostic study findings associated with malignant peripheral nerve sheath tumor.

## Biopsy
Biopsy is helpful in the diagnosis of schwannoma.

# Treatment

## Medical Therapy
In the setting of localized disease, as is the case with all soft tissue sarcomas, complete surgical extirpation with clear margins is the treatment of choice.The predominant therapy for malignant peripheral nerve sheath tumor is surgical resection.In the setting of advanced or metastatic MPNST, outcomes are generally poor. Doxorubicin and ifosfamide are the most active agents in unselected soft tissue sarcomas, with a Response Evaluation Criteria in Solid Tumors (RECIST) response rate of approximately 25% for the combination. Adjunctive chemotherapy and radiation therapy may be required.Multiple retrospective datasets have shown the negative prognostic impact of involved margins and local recurrence. As in the case with most large (>5 cm) high-grade limb sarcomas, adjuvant radiation is advocated to reduce local recurrence. The risk-benefit profile of adjuvant radiation in patients with NF1 must be carefully discussed with all patients in view of the heightened risk of radiation-induced sarcomas.

## Surgery
Surgery is the mainstay of treatment for malignant peripheral nerve sheath tumor. For patients suffering from neurofibrosarcomas in an extremity, if the tumor is vascularized 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.

## Primary Prevention
There is no established method for prevention of malignant peripheral nerve sheath tumor.

## Secondary Prevention
There are no secondary preventive measures available for malignant peripheral nerve sheath tumor.