Malignant peripheral nerve sheath tumor: models, biology, and translation

Abstract

Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are aggressive, invasive cancer that comprise around 10% of all soft tissue sarcomas and develop in about 8–13% of patients with Neurofibromatosis Type 1. They are associated with poor prognosis and are the leading cause of mortality in NF1 patients. MPNSTs can also develop sporadically or following exposure to radiation. There is currently no effective targeted therapy to treat MPNSTs and surgical removal remains the mainstay treatment. Unfortunately, surgery is not always possible due to the size and location of the tumor, thus, a better understanding of MPNST initiation and development is required to design novel therapeutics. Here, we provide an overview of MPNST biology and genetics, discuss findings regarding the developmental origin of MPNST, and summarize the various model systems employed to study MPNST. Finally, we discuss current management strategies for MPNST, as well as recent developments in translating basic research findings into potential therapies.

Epidemiology, Characteristic, and Prognostic Factors of Primary Sporadic Intradural Malignant Peripheral Nerve Sheath Tumor in the Spinal Canal: A Systematic Literature Review

“…Further study of molecular pathology is an effective way for diagnosis and treatment. In addition, the analysis of cancer stem cells and genetics in MPNSTs is helpful to design new treatment schemes ( 23 ). Spyra et al.…”

Practical Approach to Histological Diagnosis of Peripheral Nerve Sheath Tumors: An Update

“…MPNSTs represent about 5% of all sarcomas and may arise from a peripheral nerve or a pre-existing neurofibroma; in about 50% of cases, these tumors arise in the context of NF1, while in the remaining cases they appear to be sporadic (40% of cases) or associated with a previous history of radiation [ 1 , 4 , 6 , 73 , 74 , 75 ]. A significant number of the sporadic tumors arise in the deep soft tissues without any anatomic evidence of association with a peripheral nerve or pre-existing neurofibroma (soft tissue MPNST) [ 73 , 74 , 75 ]. The sporadic tumors usually occur in patients with an age ranging from 30 to 50 years, while the NF1-asociated tumors can manifest in younger patients, including in childhood [ 73 , 74 , 75 ].…”

“…A significant number of the sporadic tumors arise in the deep soft tissues without any anatomic evidence of association with a peripheral nerve or pre-existing neurofibroma (soft tissue MPNST) [ 73 , 74 , 75 ]. The sporadic tumors usually occur in patients with an age ranging from 30 to 50 years, while the NF1-asociated tumors can manifest in younger patients, including in childhood [ 73 , 74 , 75 ]. The most common sites are the extremities, trunk, and head/neck region; among the major nerves involved, the sciatic nerve is the most common one, followed by the brachial and sacral plexuses and the paraspinal nerves.…”

“…The most common subtype of MPNSTs is the classic type, basically a spindle cell sarcoma that can be divided into low- and high-grades based on the following morphological features: (i) the loss of neurofibroma architecture; (ii) hypercellularity; (iii) cytological atypia; (iv) mitotic activity; and (v) tumor necrosis [ 1 , 73 , 74 , 75 ]. Low-grade MPNSTs are uncommon (10% of all MPNSTs) and usually arise from a pre-existing NF1-associated neurofibroma ( Figure 21 ) [ 1 , 76 ].…”

Impact of Limb Salvage on Prognosis of Patients Diagnosed With Extremity Bone and Soft Tissue Sarcomas

“…In advanced diseases, the response rates to cytotoxic chemotherapy were low. In our study, the poor survival of MPNST patients receiving LSS could be attributed to the agressivity of the disease, high recurrence, and lack of chemosensibility due to mutation of the NF1 gene ( 35 , 36 ). Moreover, the landmark analysis for survivors with advanced osteosarcomas of ≥1 year revealed no effect of LSS on survival, which indicated that patients could benefit from LSS only within 1 year after sarcoma diagnosis.…”