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Presentation: 20 slides

MPNSTs are rare malignancies that are classically associated with pre-existing plexiform neurofibromas in neurofibromatosis type 1 (NF-1) patients, but also occur in association with radiation as well as sporadically in patients with no known risk factors. The typical presentation of sporadic MPNST is a new painless enlarging mass. The typical presentation of MPNST in an NF-1 patient is rapid enlargement or new onset of pain associated with a pre-existing plexiform neurofibroma. Although both MPNST and benign neurofibromas share in common the absence of neurofibromin function due to loss of both NF-1 alleles, malignant transformation to MPNST requires several additional aberrations, most notably constituent activity of the proliferative Ras GTPase pathway, increased expression of growth factor receptors such as EGFR and decreased activity in additional tumor suppressors such as p53, p16INK4A and p19ARF. Grossly, MPNSTs typically appear "fusiform" (wide in the middle with tapering at both ends), larger than 5 cm and tan-gray on cut section. Necrosis, cyst formation and a "pseudocapsule" are frequently, but not always, present features. They may or may not be surrounded by portions of a pre-existing neurofibroma which have not undergone malignant transformation. The histologic features of MPNSTs show considerable variation and they overlap greatly with benign neurofibromas. However, several features argue in favor of MPNST, including perivascular hypercellularity, hyperchromatic wavy nuclei, high mitotic activity, necrosis and only focal or no areas of S-100 positivity. MRI is the imaging modality of choice for evaluating MPNSTs. It can be useful for differentiating MPNST from benign neurofibroma based on the absence of the fascicular sign, target sign and split-fat sign. CT is most useful for detecting metastases and chest CT should be ordered for all newly diagnosed patients due to the high incidence of pulmonary metastases at the time of presentation. PET-CT has an evolving role, especially with regards to differentiating neurofibroma from MPNST based on standardized uptake value (SUV). Prognostic factors for MPNST include tumor size, local recurrence and completeness of surgical resection. There is some evidence to suggest that tumor location (extremity vs. trunk, head and neck), histologic grade, p53 expression, S-100 expression, radiation therapy and histologic subtype may also be important prognostic factors. Complete surgical tumor removal provides the only hope for cure of MPNST. There have been some cases reported where neoadjuvant radiation and/or chemotherapy have allowed for subsequent complete surgical removal and thereby enabled cure. There is considerable evidence to suggest that adjuvant radiation, but not adjuvant chemotherapy, is helpful in preventing local recurrence of MPNST. Postoperative follow-up strategies for MPNST vary greatly across practitioners. No formal guidelines for follow-up have been proposed, however one author has demonstrated that regular, frequent re-evaluation every few months with MRI can allow for timely excision of local recurrences, thereby prolonging overall survival and in some cases even extending the potential for cure.

In this presentation, I attempt to define MPNST as a clinical entity and summarize much of the current state of knowledge on the pathogenesis, gross pathology, microscopic pathology, diagnostic imaging features and treatment strategies for MPNST.