Final Diagnosis -- High-grade Sarcoma (Malignant Peripheral Nerve Sheath Tumor)




Since not all the tumors in this group are clearly schwannian in origin, malignant peripheral nerve sheath tumor (MPNST) is currently preferred term for the neoplasm previously known as malignant schwannoma, neurogenic sarcoma, and neurofibrosarcoma (1). About half of the tumors are involved by neurofibromas as part of type I neurofibromatosis (NF1), which are associated with chromosome 17p deletion and mutation of p53 gene (2). The large majority of MPNST arise in adults, but they have also been recorded in children. MPNST may occur almost anywhere, including the skin, head and neck, and retroperitoneum, but a peripheral location on the extremities is more common in the solitary form (non-NF1), whereas central lesions on the trunk or head and neck predominate in neurofibromatosis. Real malignant change in solitary schwannoma is a rare phenomenon. Grossly, the finding of a large mass producing fusiform enlargement of a major nerve, such as the sciatic nerve, is characteristic. Occasional MPNSTs are associated with pain and parasthesias, although majority of the cases are asymptomatic.

It is often difficult to make a diagnosis of MPNST on routine stains alone; the tumor may resemble a fibrosarcoma (figures 3 and 4). Because of its difficult microscopic recognition, there is agreement that the diagnosis can be made on morphologic grounds alone if attention is paid to detail. If the tumor develops in a patient with type I neurofibromatosis or the tumor is obviously arising within the anatomic compartment of a major nerve or in continuity with a neurofibroma, the diagnosis of MPNST should be the primary consideration. The morphologic features that help to confirm the diagnosis of MPNST include (a) alternating hypocellular/hypercellular regions (Figure 3 A and B), (b) the appearance of the thin, wavy, comma-shaped, or bullet-shaped nucleus (Figure 3C), (c) the presence of nuclear palisading, (d) the presence of nerve-like whorls or tactoid bodies resembling Wagner-Meissner corpuscles, and (e) prominent thick-walled vasculature. The presence of the alternating hypercellular and hypocellular areas is suggestive of nerve-sheath origin.

Consistent presence of mitoses (greater than one mitosis per 20 hpf) is also evidence of potential malignant behavior in a neurofibromatous lesion (Figure 3). Additional hint for the diagnosis of malignancy in a neurofibromas-like tumor is the presence of focal densely cellular regions and necrosis (Figures 3 and 4). In approximately half of the cases, the tumor cells show reactivity for S100 protein (3, 4). However, the immunoreactivity to S100 protein tends to be focal (Figure 6) and not particularly strong (5) unlike a spindle cell melanoma, where S100 positivity is diffuse. The tumor cells of the present case are also positive for other "neural" markers, CD99 and CD56 (Figure 6), supporting the diagnosis. Mechtersheimer and coworkers demonstrated that CD56 was detectable in 3 of 3 benign and 8 of 13 malignant schwannomas (6). In this case, presence of cytokeratin positivity also raises the possibility of a synovial sarcoma (7). However, given the morphological features, this diagnosis was not favored.

Local recurrence and distal metastases of MPNST are frequent. In general, there is little correlation between microscopic grading and prognosis. No consistent chromosomal abnormalities have been found in MPNST, although structural abnormalities of chromosomes 17 and 22 have been observed in some cases (8).


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  5. Zhou H, Coffin CM, Perkins SL, Tripp SR, Liew M, Viskochil DH. Malignant peripheral nerve sheath tumor. A comparison of grade, Immunophenotype, and cell cycle/growth. Activation marker expression in sporadic and neurofibromatosis 1-related lesions. Am J Surg Pathol 2003; 27:1337-1345.
  6. Mechtersheimer G, Staudter M, and Moller P. Expression of the natural killer cell-associated antigens CD56 and CD57 in human neural and striated muscle cells and in their tumors. Cancer Res 1991; 51:1300-1307.
  7. Smith TA, Machen SK, Fisher C, Goldblum JR. Usefulness of cytokeratin subsets for distinguishing monophasic synovial sarcoma from malignant peripheral nerve sheath tumor. Am J Clin Pathol. 1999; 112:641-648.
  8. Kehrer-Sawatzki H, Assum G, Hameister H. Molecular characterisation of t(17;22)(q11.2;q11.2) is not consistent with NF1 gene duplication. Hum Genet 2002; 111:465-467.

Contributed by Ming Yin, MD, PhD and Uma Rao, MD

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