Malignant peripheral nerve sheath tumours in inherited disease

The North West Regional Genetic Register covers a population of 4.1 million and was interrogated for incidence of MPNST in 12 cancer prone syndromes. Age, incidence and survival curves were generated for NF1.Fifty two of 1254 NF1 patients developed MPNST, with MPNST also occurring in 2/181 cases of schwannomatosis and 2/895 NF2 patients. Three cases were also noted in TP53 mutation carriers. However, there were no cases amongst 5727BRCA1/2 carriers and first degree relatives, 2029 members from Lynch syndrome families, nor amongst 447 Familial Adenomatous Polyposis, 202 Gorlin syndrome, nor 87 vHL cases.MPNST is associated with schwannomatosis and TP53 mutations and is confirmed at high frequency in NF1. It appears to be only increased in NF2 amongst those that have been irradiated. The lifetime risk of MPNST in NF1 is between 9–13%.Malignant peripheral nerve sheath tumour (MPNST) are uncommon tumours varying substantially in clinicopathologic features [1]. Previous studies have shown that 20%–50% of patients with MPNST also have Neurofibromatosis type 1 (NF1) [2-4]. Cutaneous MPNST is very rare [5-7]; skin involvement is usually secondary to local invasion or metastasis from larger underlying tumours. Most are high grade, poorly differentiated and aneuploid. Only half can be shown to exhibit schwannian differentiation by immunohistochemical methods. Tumours exhibiting mesenchymal primarily rhabdomyosarcomatous differentiation (Triton tumour) are often associated with NF1 [8]. The lifetime risk of MPNST in NF1 has previously been assessed as between 8–13% [4]. However, there has been limited evidence of association with other tumour prone disorders, with only case reports showing associations with TP53 mutations [9] and schwannomatosis [10]. We have reviewed our genetic register databases for presence of MPNST amongst affected cases and for non-syndromic conditions their first degree relatives (FDRs). The conditions studied are summarised in Table 1.The North West Re