Answer: Malignant peripheral nerve sheath tumor (MPNST)

Histology: This tumor arises in the context of a neurofibroma in a patient with a history of neurofibromatosis. The areas of neurofibroma are characterized by bland spindled cells in a delicate myxoid stroma. The superimposed sarcoma has multiple patterns. The sarcoma shows sharp linear variations in cellularity, and tumor cells become characteristically plump (epithelioid) adjacent to blood vessels. In other areas, the tumor forms tactoid bodies reminiscent of pacinian corpuscle. There are areas with a high mitotic rate and high cellularity associated with necrosis, indicating that this is a high-grade sarcoma.

Discussion: A cellular schwannoma would not show the high mitotic rate and significant necrosis demonstrated in the current lesion. A cellular schwannoma would also be diffusely positive for S100 protein, while malignant peripheral nerve sheath tumors are typically only focally immunoreactive for this marker. The distinctive features of this tumor (linear variations in cellularity, tactoid body formation, epithelioid change in association with blood vessels) suggest MPNST are not characteristic of either synovial sarcoma or fibrosarcoma.

There are several settings in which one can establish the specific diagnosis of malignant peripheral nerve sheath tumor when one is dealing with a spindle cell sarcoma. Association of the sarcoma with a peripheral nerve or with a benign nerve sheath tumor (usually neurofibroma) is presumptive evidence. A tumor occurring in a patient with NF-1 with morphological features typical of MPNST also qualifies. In the sporadic setting, a tumor morphologically typical of MPNST requires either immunohistochemical or ultrastructural evidence of schwannian or perineurial differentiation to qualify as a MPNST. The current case meets the first three criteria stated for MPNST.