Low Mitotic Rate Does Not Predict Adverse Long Term Outcome in Peripheral Nerve Sheath Tumors
S Sheth, M Bhasin, C Magyar, F Eilber, S Dry. UCLA, Los Angeles, CA
Background: Increased cellularity (IC), low mitotic rate (MR), and nuclear atypia (NA) are described features of low grade malignant peripheral nerve sheath tumors (MPNSTs). However, specific criteria remain elusive. The clinical significance of low MR in neurofibromas (NFs), especially with other atypical features such as IC or NA, is not well established. Herein, we present the largest known series of PNSTs with low MR and extended clinical follow up.
Design: Materials from 14 patients diagnosed with either low grade MPNST or NF with mitotic activity (PNSTmit) were analyzed. For comparison, we studied 5 high grade MPNSTs and 7 NFs without mitoses (NFno). All had clinical follow up data. Proliferative indices (max. MR/50 HPFs, Ki-67, p53), NA, and cellularity were noted. Maximum MR/50HPF on H&E or PHH3 staining was used. Cellularity, Ki-67 and p53 indices were estimated and also quantified by automated image analysis software. Tumors with >10% p53 nuclear staining were classified as positive.
Results: Fourteen patients (9F,5M), 33-72 years old (mean 47) with tumors 2.015.5 cm in size (mean 5.1 cm) comprised the PNSTmit group. Neurofibromatosis type 1 (NF1) affected 5; one patient with a plexiform NF lacked a definite diagnosis of NF1. All had conservative excision and 4 patients, 2 of which had positive margins, received post-operative radiation. All tumors contained mitoses ranging from 1-6/50 HPFs. The mean Ki-67 rate was 1.3% (0.1-5.2%). All tumors were p53 negative. Twelve tumors had NA (5 diffuse) and 10 had IC. NA included pleomorphism, increased size, and dark smudgy chromatin. No aggressive local recurrences (LR) or distant metastases (DM) were seen during a mean 42 months of follow up (range 8-156). One NF1 patient with positive margins had a histologically similar LR at 156 months. There were no significant differences in clinical features, Ki-67, or p53 between the PNSTmit and NFno groups (two way ANOVA). In contrast, 5 high grade MPNSTs had significantly higher MR (mean 184/50 HPF, range 158-295/50 HPF) and Ki-67 rate (20.9%, range 7.5-36.7%) than PNSTmit or NFno (both p<0.001 on 2 way ANOVA). Four MPNST patients had LRs and 2 developed DM; one patient died of disease, one is alive with disease, and 3 are without disease (mean 29 months follow up; range 15-84).
Conclusions: In this series of PNSTs, low MR (<6 mitoses/50 HPF) was not associated with aggressive clinical behavior, even in the setting of IC, NA, or NF1. A low Ki-67 rate (<5%) was seen in all tumors. Longer follow up and additional cases will be needed to confirm our findings.
Category: Bone & Soft Tissue
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 19, Monday Morning