Malignant peripheral nerve sheath tumors (MPNSTs) are forms of peripheral nerve sheath tumors and comprise of malignant forms of neurofibromas and schwannomas. Approximately half of such tumors are seen in individuals with neurofibromatosis type I (NF1), in such cases arising from pre-existing neurofibromas.
Malignant peripheral nerve sheath tumors are estimated to account for 5-10% of all soft-tissue sarcomas. They typically present in young and middle-aged adults 8. There is no recognized gender predilection. When seen in the setting of NF1, they tend to occur in younger patients 8. They are also encountered with greater frequency in individuals who have previously received radiotherapy 8.
Clinical presentation varies dependent on location.
MPNSTs can either arise de-novo or de-differentiate from an existing neurofibroma (most often plexiform neurofibromas in NF1) or rarely other neurogenic tumors (e.g schwannoma, ganglioneuroblastoma, ganglioneuroma, pheochromocytoma) 8.
MPNSTs usually arise from a large nerve, and thus usually occur close to a plexus (e.g. sacral plexus/brachial plexus). Cranial nerves are rarely involved, and on the rare occasions they are, then the MPNST has usually arisen from an underlying schwannoma rather than a neurofibroma 8.
Most MPNSTs demonstrate inactivation of a number of genes: NF1, CDKN2A and PRC2 8.
The macroscopic appearance depends both on location and on whether or not the MPNST has arisen from an underlying pre-existing tumor. They are often large (>5cm) at diagnosis, and may demonstrate local infiltration into surrounding tissues 8.
The microscopic appearance of MPNSTs is heterogeneous, varying in cellularity and growth pattern, generally including tightly packed spindle cells arranged in either a herringbone or interwoven fasciculated pattern 8.
Immunohistochemistry reflects their neurogenic origin, with the following immunoreactivity 8:
- S100: positive in 50-70% - low in high-grade MPNSTs
- p53 protein: positive in 75%
- EGFR: positive in ~35%
A number of histological variants are recognized 8:
- epithelioid MPNST
- MPNST with divergent differentiation (aka malignant triton tumor)
- MPNST with perineural differentiation (aka malignant perineurioma)
Imaging criteria are generally considered unreliable in differentiating from a more benign neurofibroma or schwannoma 4. However, general rules favoring an MPNST include:
- the larger the lesion, the more likely for it to be malignant
- irregular borders (although most MPNSTs can have well-defined margins)
- rapid growth in interval imaging
- usually isointense to muscle 4
- a heterogeneous signal on T1 (if present) may useful in differentiating from a neurofibroma 3
- can have low signal due to high collagen content 4
Gallium67 scintigraphy may show higher uptake than that of a neurofibroma 6-7.
Treatment and prognosis
It is an aggressive tumor that carries a poor prognosis, with 20-25% of patients developing metastases 8. Poor prognostic factors include 8:
- large size
- location on the trunk
- high-grade histological features
- 1. Ogose A, Hotta T, Morita T et-al. Diagnosis of peripheral nerve sheath tumors around the pelvis. Jpn. J. Clin. Oncol. 2004;34 (7): 405-13. doi:10.1093/jjco/hyh072 - Pubmed citation
- 2. Lee JH, Lee HK, Choi CG et-al. Malignant peripheral nerve sheath tumor in the parapharyngeal space: tumor spread through the eustachian tube. AJNR Am J Neuroradiol. 2001;22 (4): 748-50. AJNR Am J Neuroradiol (full text) - Pubmed citation
- 3. Wasa J, Nishida Y, Tsukushi S et-al. MRI features in the differentiation of malignant peripheral nerve sheath tumors and neurofibromas. AJR Am J Roentgenol. 2010;194 (6): 1568-74. doi:10.2214/AJR.09.2724 - Pubmed citation
- 4. Rha SE, Byun JY, Jung SE et-al. Neurogenic tumors in the abdomen: tumor types and imaging characteristics. Radiographics. 23 (1): 29-43. doi:10.1148/rg.231025050 - Pubmed citation
- 5. Murphey MD, Smith WS, Smith SE et-al. From the archives of the AFIP. Imaging of musculoskeletal neurogenic tumors: radiologic-pathologic correlation. Radiographics. 19 (5): 1253-80. Radiographics (full text) - Pubmed citation
- 6. Hrehorovich PA, Franke HR, Maximin S et-al. Malignant peripheral nerve sheath tumor. Radiographics. 23 (3): 790-4. doi:10.1148/rg.233025153 - Pubmed citation
- 7. Levine E, Huntrakoon M, Wetzel LH. Malignant nerve-sheath neoplasms in neurofibromatosis: distinction from benign tumors by using imaging techniques. AJR Am J Roentgenol. 1987;149 (5): 1059-64. AJR Am J Roentgenol (abstract) - Pubmed citation
- 8. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK "WHO Classification of Tumours of the Central Nervous System. 4th Edition Revised" ISBN: 9789283244929