Prevalence, treatment and survival of Malignant Peripheral Nerve Sheath Tumor in the Danish neurofibromatosis type 1 population

PURPOSE: While neurofibromatosis type 1 (NF1)-associated malignant peripheral nerve sheath tumor (nfMPNST) is often considered to have a particularly poor prognosis compared to sporadic malignant peripheral nerve sheath tumor (sMPNST), this assumption remains insufficiently substantiated. This study aimed to compare clinical characteristics, treatment outcome, and survival between nfMPNST and sMPNST in a nationwide Danish cohort. PATIENT AND METHOD: We conducted a retrospective cohort study of patients with malignant peripheral nerve sheath tumor (MPNST) in Denmark from 2000 to 2020. NF1-associated cases were identified through a national NF1 registry, while sporadic cases of MPNST were extracted from the Danish Sarcoma Database. Clinical, pathological, and treatment data were supplemented by chart review and national pathology records. Survival outcomes were analysed using Kaplan-Meier estimates and Cox proportional hazards models. RESULTS: A total of 146 patients were included of which 42 had nfMPNST and 104 sMPNST. Patients with nfMPNST were significantly younger at diagnosis (median 37 (min-max: 12-73) vs. 58 (min-max: 5-93) years, p < 0.001) and had larger tumors (>5 cm in 88% vs. 50%, p < 0.001). Wide margin resection was achieved less often in nfMPNST (35% vs. 66%, P = 0.003), and adjuvant radiotherapy was more commonly administered (61% vs. 36%). Five-year overall survival for localized disease was significantly lower in nfMPNST (44% vs. 63%, P = 0.03), with higher recurrence rates (69% vs. 49%, P = 0.049) and shorter time to recurrence (median 2.2 vs 3.4 years) Among 27 sMPNST tumors analysed by next-generations sequencing, 5 (19%) harbored pathogenic NF1 variants. CONCLUSION: nfMPNST presents at a younger age with more aggressive features and worse outcomes compared to sporadic cases. These findings support the need for tailored surveillance and treatment strategies in NF1 patients and highlight the potential role of NF1 alterations in sMPNST pathogenesis.