Brain Pathology Case of the Month - March 2013

DIAGNOSIS

MALIGNANT PERIPHERAL NERVE SHEATH TUMOR

DISCUSSION

Malignant peripheral nerve sheath tumor (MPNST) is a malignant spindle cell neoplasm which accounts for 5-10% of all soft tissue sarcomas. MPNST is thought to arise from various elements of the nerve sheath (particularly the Schwann cell) and often, but not always, arises from a peripheral nerve. MPNST may occur spontaneously or in association with Neurofibromatosis Type 1 (NF1). Roughly 25%-50% of MPNST occur in patients with NF1.7 Most MPNSTs are associated with a major nerve trunk and present as enlarging masses. Clinical symptoms vary depending on location. Although MPNST has been described in childhood, its incidence is rare. Intracerebral MPNST is even rarer, and has been divided into those tumors that are associated with cranial nerves, and those which are not (such as our case). There have been a total of 18 reported cases of MPNST not associated with cranial nerves,2 excluding our case.

Radiologic findings in intracerebral MPNST include a mass in any part of the cerebrum, which usually has marked surrounding edema. Histologically, the mass is a spindled, highly cellular lesion with marked nuclear pleomorphism, prominent nucleoli, and brisk mitotic activity. The overall architecture often resembles that of a fibrosarcoma, but with less organization; MPNST may show marbling or herringbone arrangements. The immunohistochemical profile is also variable, although most MPNSTs are immunopositive for vimentin, S-100 protein, p53 and nestin, and are almost always negative for keratins. CD34 may occasionally be expressed in MPNST.

Because of the variability in histologic and immunostain profiles, the diagnosis of MPNST is often challenging. In this case, several differential diagnoses were considered, including monophasic synovial sarcoma (MSS), malignant solitary fibrous tumor (MSFT), fibrosarcoma, and other high-grade sarcomas. Briefly, a high grade glioma was considered, but a glioma is almost never as sharply demarcated from adjacent pieces of brain as this tumor is. The possibility of a glioma diagnosis is further ruled out by negative immunostains for GFAP and S100 protein. Negative immunostains for desmin, smooth muscle actin, and skeletal muscle actin helped to rule out diagnoses of leiomyosarcoma and rhabdomyosarcoma, and negative immunostains for CK and EMA ruled down a diagnosis of MSS, most of which have at least a little expression of one or both of these markers. A CD31 and CD34 were both negative in the tumor cells, ruling out MSFT. A strongly positive CD56 (NCAM) immunostain argued against a diagnosis of fibrosarcoma, which is considered a diagnosis of exclusion, and favored a diagnosis of MPNST or MSS. A strongly positive p53 favored MPNST, and a strongly positive nestin in this context established the diagnosis of MPNST.3.5

Intracerebral MPNST is presumed to arise from peripheral nerves which traverse the cerebral white matter, probably with blood vessels. Several possibilities for the origin of these peripheral nerves exist. It is known that Schwann cells accompany peripheral nerves in the dura and may penetrate the brain alongside the blood vessels they accompany. It is conceivable, therefore, that a Schwann cell tumor could originate from an intracerebral perivascular nerve. Additional hypotheses include MPNST arising from adrenergic nerve fibers, pluripotential cells within the brain, displaced neural crest cells, and meningeal branches of the trigeminal nerve.2.,4 MPNST is a highly aggressive tumor with a generally poor prognosis. The addition of adjuvant therapies has improved survival, but even so, the 5-year survival rate is 52%, and the rate drops lower if good surgical margins cannot be achieved.7 For intracranial MPNST, the reported median overall survival is 9 months,1 and patients with NF1 have an even lower survival rate.8 Therapy for intracranial MPNST includes gross total resection as well as adjuvant radiation therapy, although treatment is not standardized. Chemotherapy is used in patients with systemic recurrence.6 Interestingly, a recent study found that females are less likely to develop intracranial MPNST and if they do, they have a better prognosis.1

REFERENCES

  1. Gousias, K, Bostrom, J, Kovacs, A, Niehusmann, P., Wagner, I., Kristof, R. (2010) Factors of influence upon overall survival in the treatment of intracranial MPNSTs. Review of the literature and report of a case. Radiation Oncology. 5: 114-121.
  2. Munckhof, P, Germans, M, Schouten-van Meeteran, A, Oldenburger, F., Troost, D., Vandertop, P. (2011) Recurring Intracranial Malignant Peripheral Nerve Sheath Tumor: Case Report and Systematic Review of the Literature. Neurosurgery. 68: E1152-E1159.
  3. Olsen, S, Thomas, D, Lucas, D (2006) Cluster Analysis of Immunohistochemical Profiles in synovial sarcoma, malignant peripheral nerve sheath tumor, and Ewing sarcoma. Modern Pathology. 19: 659-668.
  4. Scheithauer, B, Erdogan, S, Rodriguez, F, Burger, P.C., Woodruff, J.M., Kros, J.M., Gokden, M., Spinner, R.J. (2009) Malignant Peripheral Nerve Sheath Tumors of Cranial nerves and Intracranial Contents: A Clinicopathologic Study of 17 Cases. American Journal of Surgical Pathology 33: 325-338.
  5. Shimada, S, Tsuzuki, T, Kuroda, M, Nagasaka, T., Hara, K., Takahashi, E., Hayakawa, S., Ono, K., Maeda, N., Mori, N., Illei, PB. (2007) Nestin expression as a new marker in malignant peripheral nerve sheath tumor. Pathology International. 57: 60-67.
  6. Tamarit, M, Navarro, R, Alcazar, L (2010) Malignant peripheral nerve sheath tumor of the infratemporal fossa with intracranial extension. Ear, Nose & Throat Journal. 89: 596-599.
  7. Weiss, S., Goldblum, J. (2008) Enzinger and Weiss's Soft Tissue Tumors. 5th Ed. Mosby Elsevier.
  8. Ziadi, A, Saliba, I (2010) Malignant peripheral nerve sheath tumor of intracranial nerve: A case series review. Auris Nasus Larynx. 37:539-545.

Contributed by Jamie L. Odem, Gustavo Matute Turizo, Douglas C. Miller

International Society of Neuropathology