Clinical Review & Education

Images in Neurology

Malignant Peripheral Nerve Sheath Tumor in Neurofibromatosis Type 1 John P. Rossiter, MB, BCh, PhD; Paul V. Fenton, MD

A young adult man with neurofibromatosis type 1 (NF1) presented with a several-month history of an increasingly painful mass in the posteroinferior region of the right thigh. Imaging studies (Figure) showed a relatively well-circumscribed mass, 15 cm in length and 7 cm in diameter, arising on a background of very extensive involvement of the peripheral nervous system by plexiform neurofibromas. A biopsy specimen of the mass showed a high-grade (World Health Organization grade IV) malignant peripheral nerve sheath tumor (MPNST). An above-knee amputation was subsequently performed and the MPNST (Figure, inset A) was found to arise in continuity with one of the many preexisting low-grade (World Health Organization grade I) plexiform neurofibromas (Figure, inset B shows an example of such in the leg). For approximately 3.5 years following surgery and radiotherapy, there was no evidence of local tumor recurrence. The patient then was seen with a large left-sided retroperitoneal mass that was histopathologically confirmed to also be an MPNST, possibly a metastasis from the original thigh tumor but more likely a de novo primary tumor. He subsequently underwent several major debulking surgeries, radiotherapy, and rounds of chemotherapy, including palliative doxorubicin, for increasingly disseminated metastatic disease. He died approximately 7 years after his initial presentation.

Figure. Coronal T1-Weighted Magnetic Resonance Images of the Pelvis/Upper Thighs and the Lower Thighs/Legs Show Extensive Bilateral Plexiform Neurofibromas and a 15×7 cm Mass in the Lower Right Thigh



Discussion Neurofibromatosis type 1 is an autosomal dominant syndrome resulting from a diverse range of mutations in the NF1 gene, with approximately 50% of affected individuals having a de novo mutation.1 Plexiform neurofibromas are an important diagnostic feature of NF1 and are found in approximately half of people with NF1. In NF1, MPNST (previously termed neurofibrosarcoma) typically arises on a background of a preexisting neurofibroma, especially a plexiform neurofibroma, with local pain and/or rapid growth being important clinical indicators.2 Individuals with NF1 have an approximately 10% lifetime risk of developing MPNST, most commonly in the third or fourth decades of life,2 and following diagnosis have an overall 5-year survival rate of approximately 33%.3

ARTICLE INFORMATION Author Affiliations: Department of Pathology and Molecular Medicine, Queen’s University and Kingston General Hospital, Kingston, Ontario, Canada (Rossiter); Department of Diagnostic Radiology, Queen’s University and Kingston General Hospital, Kingston, Ontario, Canada (Fenton). Corresponding Author: John P. Rossiter, MB, BCh, PhD, Department of Pathology and Molecular Medicine, Queen’s University and Kingston General


(The upper and lower magnetic resonance images are from closely adjacent, but not identical, coronal planes. This is because the plexiform neurofibromas in the pelvis and upper thighs are more clearly demonstrated in the slice shown. As a consequence of the different planes, there is a partial mismatch in the alignment of the thighs between the 2 images and the lower image has been slightly reduced in size to minimize this.) Microscopic image A shows a representative area of the highly cellular and mitotically active malignant peripheral nerve sheath tumor and image B shows low-density spindle-shaped tumor cells in a stroma comprising bundles of wavy collagen fibers, characteristic of neurofibroma (insets A and B, hematoxylin phloxine saffron, original magnification ×40).

Hospital, Richardson Laboratory, 88 Stuart St, Kingston, ON K7L 3N6, Canada ([email protected]


Accepted for Publication: December 4, 2012.

2. Jett K, Friedman JM. Clinical and genetic aspects of neurofibromatosis 1. Genet Med. 2010;12(1):1-11.

Published Online: December 16, 2013. doi:10.1001/jamaneurol.2013.2048. Conflict of Interest Disclosures: None reported.

1. Korf BR. Malignancy in neurofibromatosis type 1. Oncologist. 2000;5(6):477-485.

3. Porter DE, Prasad V, Foster L, Dall GF, Birch R, Grimer RJ. Survival in malignant peripheral nerve sheath tumours. Sarcoma. 2009;2009:756395.

JAMA Neurology February 2014 Volume 71, Number 2

Copyright 2014 American Medical Association. All rights reserved.

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Malignant peripheral nerve sheath tumor in neurofibromatosis type 1.

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