Definition: Malignant tumor arising from peripheral nervous tissue or showing nerve sheath differenciation.
Malignant peripheral nerve sheath tumors (MPNSTs) are uncommon soft tissue malignancy and usually arise from peripheral nerves or somatic soft tissues. 70% are associated with neurofibromatosis type 1 (NF1), the most common familial cancer- predisposing syndrome in humans. They account for about 5% of all malignant soft tissue tumors.
Malignant peripheral nerve sheath tumor (MPNST) is defined as a malignant tumor arising from or differentiating toward cells of the nerve sheath. The majority arise either de novo or from preexistent nerve sheath tumors, usually an intraneural or plexiform neurofibroma.
Only rare examples arise in transition from schwannoma, ganglioneuroma, or paraganglioma/pheochromocytoma. The latter have not been reported to be precursors of cranial nerve MPNST.
The term malignant peripheral nerve sheath tumor is the generally agreed upon designation for all malignant tumors arising in transition from either neurofibroma, schwannoma, or de novo from peripheral nerve sheath. This includes tumors that are Schwann or perineurial cell derived or show such differentiation. Most MPNST involve spinal nerves of the trunk, limbs, and major plexuses.
Clinical setting
- sporadic :
- peak onset in the fifth decade
- 30-50% associated with neurofibromatosis type 1 (NF1):
- inactivating NF1 gene mutations, with increased ras signaling and subsequent increased risk of developing both benign and malignant tumors, especially peripheral nerve sheath tumors (2% lifetime risk of MPNST)
- MPNST is difficult to detect clinically in NF1 patients
- poor prognosis (high likelihood of local recurrence and distant metastasis)
- rarely arises from a benign schwannoma or a ganglioneuroma
Predisposition
MPNST is a complication of NF1 and approximately 4% of patients with NF1 develop MPNSTs, compared with an incidence rate of 0.001% in the general population.
Localisation
buttock and thigh
brachial plexus and upper arm
paraspinal region
cranial nerves and intracranial contents (malignant peripheral nerve sheath tumors of cranial nerves and intracranial contents)
Gross findings
- classic form : large fusiform or eccentric mass in a major nerve
- fleshy white-tan surface, with areasof secondary hemorrhage and necrosis
Histology
- fasciculated growth pattern, with alternance of dense and hypodense fascicles
- spindle cells, nuclei with tapered ends and wavy or buckled configuration
- perivascular accentuation and infiltration of vessel walls
- frequent mitoses
- possible heterologous differenciation (bone, cartilage etc.)
- rhabdomyosarcomatous component : malignant Triton tumor
Variants
- epitheliod MPNST
- pigmented (melanotic) MPNST
- plexiform MPNST (6638259)
- malignant Triton tumor
Immunohistochemistry
- 50% are S-100 protein positive (positivity in less than 20-30% of cells)
- EMA positivity if perineurial differenciation
- synchronous presence of p53, p16, and p27 alterations, decreased S-100 protein, Leu 7, and CD34 immunoreactivity patterns, and increased proliferation markers Mib-1 and TopoII[alpha] in high-grade MPNST
Differential diagnosis
plexiform cellular schwannoma - multinodular cellular schwannoma (14508393)
Cytogenetics
t(2;4)(q35;q31) (12935926)
t(X;12)(q22;q24) (12935926)
References
Am J Surg Pathol. 2003 Oct;27(10):1337-45 (14508395)
Wanebo JE, Malik JM, VandenBerg SR, Wanebo HJ, Driesen N, Persing JA. Malignant peripheral nerve sheath tumors. A clinicopathologic study of 28 cases. Cancer. 1993. 71(4): 1247-1253.
Baehring JM, Betensky RA, Batchelor TT. Malignant peripheral nerve sheath tumor: the clinical spectrum and outcome of treatment. Neurology. 2003. 61(5): 696-8.
Baehring JM, Betensky RA, Batchelor TT. Malignant peripheral nerve sheath tumor: the clinical spectrum and outcome of treatment. Neurology. 2003. 61(5): 696-698.
Kourea HP, Bilsky MH, Leung DH, Lewis JJ, Woodruff JM. Subdiaphragmatic and intrathoracic paraspinal malignant peripheral nerve sheath tumors: a clinicopathologic study of 25 patients and 26 tumors. Cancer. 1998. 82(11): 2191-2203.
Wong WW, Hirose T, Scheithauer BW, Schild SE, Gunderson LL. Malignant peripheral nerve sheath tumor: analysis of treatment outcome. Int J Radiat Oncol Biol Phys. 1998. 42(2): 351-360.
