Favorable Outcome of Early Malignant Peripheral Nerve Sheath Tumor (MPNST) Arising in Neurofibroma
Darya Buehler, Steven D Billings, John R Goldblum, Brian P Rubin. Cleveland Clinic, Cleveland, OH
Background: Early MPNST arising in a neurofibroma (NF) is typically diagnosed based on proposed recommendations including hypercellularity, fascicles, nuclear enlargement, diffuse cytologic atypia and mitoses. Little data is available to determine if these transitioning tumors behave in the same manner as conventional MPNSTs.
Design: In this preliminary study blinded to outcomes, we histologically re-evaluated a panel of nerve sheath tumors previously diagnosed as early MPNST arising in a NF (eMNF) along with a control group of deep-seated NFs. We evaluated hypercellularity, hypocellular (<50%) and hypercellular (>50% cell to stroma ratio) fascicles, nuclear enlargement (nuclei 3x the size of neurofibroma nuclei), diffuse cytologic atypia, coarse chromatin, necrosis and mitoses. The extent of MPNST changes relative to the background NF was estimated. Only cases with a clearly identifiable NF-eMNF interface were included. Isolated hypercellularity or cytologic atypia was not considered sufficient for the diagnosis of eMNF. Cases easily recognized as morphologically high grade MPNST were excluded. Clinical follow-up was obtained.
Results: 11 eMNFs and 11 deep-seated NFs were compared. There was a history of neurofibromatosis in 7 eMNFs and 5 NFs. The following observations were recorded in the eMNF group: increased cellularity (11), hypocellular fascicles (10), hypercellular fascicles (9), nuclear enlargement (4), coarse chromatin (8), necrosis (3), mitoses (8), range 1 to 30 per hpf. Changes suggestive of eMNF comprised from 8 to 80% (mean, 44%) of the background NF. Mean clinical follow up was 34.6 months (range, 9-69 mo). Only two patients died of MPNST, both from eMNFs showing hypercellular fascicles, necrosis, coarse chromatin, mitotic figures, and in one case, diffuse cytologic atypia. All other patients were alive and none had recurrence or metastasis. Deep-seated NFs showed increased cellularity (6), rare hypocellular fascicles (2), scattered cytologic atypia (2) and nuclear enlargement (1) but not hypercellular fascicles, mitotic figures, necrosis or diffuse cytologic atypia.
Conclusions: Historically, patients with MPNST have a 30-60% five year overall survival. Although this is a retrospective analysis with a limited number of cases, it indicates a favorable outcome in most patients with eMNF. These data suggest that the malignant potential of eMNFs may be less than classical MPNST, and larger scale studies are necessary to determine whether these lesions warrant classification as MPNST or whether a classification such as nerve sheath tumor of uncertain malignant potential might be more appropriate.
Category: Bone & Soft Tissue
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 19, Tuesday Afternoon