Malignant Peripheral Nerve Sheath Tumor

Epidemiology

• Account for 5-10% of soft tissue tumors
• Majority arise de novo or from neurofibromas; prior RT (median 15 years ago) a risk factor

Pathology

• Normal nerve sheath: Schwann cells, perineural cells, fibroblasts, endothelial cells, pericytes, epineural lipocytes
• MPNSTs - Malignant tumors arising from or differentiating toward cells of peripheral nerve sheath; resemble fibrosarcomas in their basic organization
• Criteria (one of the following):
  • arise from peripheral nerve
  • arise from pre-existing benign nerve sheath tumor (e.g., neurofibroma)
  • displays a constellation of histologic features seen above, and reflecting Schwann cell differentiation
• Cytogenetics
  • Loss of NF1 gene (neurofibromin) and high levels of RAS activity; necessary but not sufficient
  • In addition, p27-Kip1, p53, or p16

Treatment Overview

• Literature mostly consists of small series or case reports
• Primary treatment is surgery
• RT appears beneficial in local control, but has no impact on long-term survival. Dose >60 Gy preferred
• Chemotherapy does not appear very effective

Outcomes

• MGH 1991-2001 PMID 12963767 -- "Malignant peripheral nerve sheath tumor: the clinical spectrum and outcome of treatment." (Baehring JM, Neurology. 2003 Sep 9;61(5):696-8.)
  • Retrospective. 54 patients. Median f/u 54 months
  • Median survival: 66 months
  • Local recurrence: 26% after median 22 months; Distant recurrence: 20%
  • Univariate factors: tumor diameter <5 cm (HR 0.4), total resection, lower age
  • Multivariate factors: extent of surgery, RT (HR 0.22), age, chemo (but caution: small sample size)

• Mayo 1975-1993 PMID 9788415 -- "Malignant peripheral nerve sheath tumor: analysis of treatment outcome. (Wong WW, Int J Radiat Oncol Biol Phys. 1998 Sep 1;42(2):351-60.)
  • Retrospective. 134 patients, 27% extremities, 73% non-extremities. Median f/u 53 months
  • Path: 10% Grade I, 32% Grade II, 32% Grade III, 24% Grade IV
  • RT (54%): 3-5 cm margins, no attempt to include LNs; 10% BT prescribed median 15 Gy to target volume
  • 5-year OS (10-year OS): 52% (34%). Median survival 61 months. RT did not affect 5-year survival (58% RT vs. 43% no RT)
  • Survival predictors: prior XRT, surgical margins
  • Local control: surgical margins, RT dose, use of IOERT/BT
  • Distant control: tumor size, grade, histologic subtype
  • Conclusion: Goal resection with negative margins. Adjuvant RT >=60 Gy, and inclusion of IOERT/BT provides improved local control

• St. Jude 1995 PMID 8591083 -- "Malignant peripheral nerve sheath tumors: the St. Jude Children's Research Hospital experience." (DeCou JM, Ann Surg Oncol. 1995 Nov;2(6):524-9.)
  • Retrospective. 28 patients treated over 30 years. 45% extremity, 34% trunk, 21% head/neck
  • 5-year OS: 39% (resectable 65%, nonresectable 0% and median 12 months)
  • Survival predictors: surgical margins, sarcoma IRS group
  • Role for RT: authors recommend only for +margins

Review

• Zurich (Switzerland) 2005 -- PMID 16442014 "Malignant peripheral nerve sheath tumors: an update." (Fuchs B, J Surg Orthop Adv. 2005 Winter;14(4):168-74.)

Malignant Intracranial Nerve Sheath Tumor

• Historically also called malignant Schwannoma, but Malignant Intracranial Nerve Sheath Tumor preferred, since it is not yet clear whether these tumors truly arise from Schwann cells
• Only 5 cases reported in literature:
  • 2/5 patients were disease-free 17 and 19 months after surgery
  • 3/5 patients recurred (5 months (death 9 months), 10 months (death 18 monts), and last had 3rd recurrence 5 years after surgery)

• Saint-Etienne (France) 2004 PMID 14744297 -- "Malignant nerve sheath tumor of the right cerebral peduncle: case report." (Beauchesne P, Neurosurgery. 2004 Feb;54(2):500-3; discussion 503-4.)
  • Case report. 35 yo man with right cerebral peduncle tumor
  • Treated with stereotactic biopsy and cranial RT to 56.25 Gy in 24 fractions
  • After recurrence, treated with doxorubicin with mild benefit
  • OS: 29 months (recurred 24 months after initial treatment)

• NYU 1998 PMID 9452273 -- "Malignant intracerebral nerve sheath tumor: a case report and review of the literature." (Sharma S, Cancer. 1998 Feb 1;82(3):545-52.)
  • Case report. 8 yo girl with right posterior temporal lobe tumor
  • Treated with surgery. RT appears to have been used, but no information provided
  • OS: healthy recurrence-free 17 months after surgery

• Abstract -- "Immunocytochemistry of recurring intracerebral nerve sheath tumour." (Bruner JM, J Neuropathol Exp Neurol 43: 296, 1984 (abstr).)