The predisposition to the development of malignant neoplasia, and particularly MPNST, in NF1 is well known. Before 2002, it was generally thought that the lifetime risk of developing MPNST in patients with NF1 was low. This was based on finding only 1–2% of patients with NF1 with MPNST in cross‐sectional studies.1
However, this might be an underestimate of the lifetime risk, because it is based on the percentage of patients with NF1 who are affected with MPNST at any one time and does not take into account loss of affected individuals from the cohort because of early death.
In 2002, Evans et al7
attempted to achieve full ascertainment of coexistent diagnoses of MPNST and NF1 over a 13‐year period and, using accepted values for the incidence and prevalence of NF1 in the population, to calculate the lifetime risk of developing MPNST in patients with NF1. In their study, they estimated a lifetime risk of 8–13%. This study has shown the lifetime risk to be around 5.9–10.3% in the Scottish cohort using the same statistical method as Evans. This estimated figure is smaller than that of Evans et al,7
but would have been very similar, had we assumed the same life span as Evans et al7
in their study.
This is the minimum lifetime risk, as there may have been further cases of coexistent diagnoses of MPNST and NF1 where the medical records were not accessible. This is illustrated by the fact that two of the cases of coexistent MPNST and NF1 were not recorded in the SCR but only in the genetics case notes. This may be because of a delay in coding and recording data, or because of alternative terminology being used in reporting histology, but the SCR estimated that at least 95% of MPNST diagnosed between 1993 and 2002 would have been registered at the time of data collection (personal communication). In addition, the genetics departments would not routinely see all individuals affected by NF1; hence, there may be further cases of coexistent diagnoses within the study period and area that have been missed.
The mean age at diagnosis of MPNST in patients with NF1 in our study was 42.1 years. In the study of Evans et al,7
the median age at diagnosis was 26 years, compared with 38 years in our study. This difference is probably due to the small number of patients involved in each study. The range of age at diagnosis in our study was 22–73 years, which was very similar to the range of 16–77 years found by Evans et al
The difference in survival from MPNST in patients with NF1 when compared with sporadic MPNST has been noted previously,7,8,12,13
and our study found a striking difference in the 5‐year survival. Evans et al
calculated a 5‐year survival of 42% in sporadic cases of MPNST and 21% in patients with a coexistent diagnosis.7
In our study, the 5‐year survival in patients with sporadic MPNST was 54%, compared with 0% in those with a coexistent diagnosis. The Kaplan–Meier curves are striking, and a 0% 5‐year survival from MPNST in patients with NF1 is a major concern. This may be because patients with NF1 present later, as they are accustomed to developing new lumps and therefore have a higher consulting threshold than the general population, or it may be that MPNST has a more aggressive course in NF1. There may also be an element of bias towards those surviving for a shorter time, because of the necessity of obtaining consent from patients who are still alive, some of whom refused consent or did not reply. There is no reason, however, why this should have more effect on the NF1 group than on the group of sporadic cases.
A recent study identified microdeletions in the NF1 region in 23.7% of patients with a coexistent diagnosis of MPNST and NF1. This is significantly greater than the accepted microdeletion frequency of 5–10% in the NF1 population, and the authors deduced that MPNST is approximately twice as common in patients with NF1 with a microdeletion as in those with an alternative mutation on the NF
Patients who have received radiotherapy,7,8
have NF1 neuropathy15
or have internal plexiform neurofibromatosis16
are also thought to be at an increased risk of developing MPNST.
- We have estimated the lifetime risk of malignant peripheral nerve sheath tumour (MPNST) in patients with neurofibromatosis type 1 (NF1) to be 5.9–10.3%, which is further evidence that it is greater than what was thought previously.
- Our study gives further evidence that survival after diagnosis of MPNST is shorter in patients with NF1 compared with patients without NF1.
- All patients with NF1 should seek specialist advice about suspicious symptoms, and current research indicates that there may be particular subgroups requiring regular surveillance.