Enrico Martin

14 Chapter 1 Grading and staging of MPNST The use of current grading and staging systems in MPNST is debated. Such systems could aid prognostication and impact treatment allocation. STS are commonly staged by the American Joint Committee of Cancer (AJCC) staging system for STS ( Table 1 ). The AJCC staging system is however of minor prognostic value in MPNST. 3,5,6 Histological grading for STS including MPNSTs are done according to the Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grading system ( Table 2 ). The FNCLCC is widely used, but has only been shown to differentiate prognosis in MPNSTs between grade 1 and 3 in one study. 15 Hence, current staging and grading systems do not seem to be of great prognostic value in MPNST. Low-grade MPNSTs according to either AJCC or FNCLCC make up less than 10% of patients with yet an unclear group of intermediate grade MPNSTs. NF1-related tumors complicate the matter further, as (plexiform) neurofibromas may transition into MPNSTs ( Table 3 ). So-called atypical neurofibromas/ atypical neurofibromatous neoplasms of uncertain biological potential (ANNUBP) may show mitoses as well and can be seen as a transitional state before becoming truly malignant. 29 When more than 3 mitoses per 10 high-power fields are seen one should consider it a low-grade MPNST according to a recent consensus overview. Table 1 American Joint Committee on Cancer soft tissue sarcoma staging system 8 th edition. Grade Definition Grade 1 Any well-differentiated tumor Grade 2 Moderate to poorly differentiated tumor ≤5cm Grade 3 Moderate to poorly differentiated tumor >5cm Grade 4 Any metastatic tumor cm: centimeter Risk factors Staging MPNSTs is thus difficult as most MPNSTs are high-grade and can present and behave differently. Additional risk factors should therefore possibly be taken into account. Until now risk factors in MPNST have varyingly been reported in literature, including the effect of tumor site, tumor depth, age, NF1 status, and treatment-related factors. 3–6,10–12 NF1 status is notably the most debated risk factor as many authors proposed a negative influence of NF1 disease on survival, yet a meta-analysis in 2012 contradicted this phenomenon for studies published after 2000. 30 Ever since, there has been one large study in adult patients still suggesting a negative influence of NF1 disease nevertheless. 6 In children specifically, risk factors have been studied even less commonly. Yet most reported presence of NF1 disease to have a worse prognosis independent of other factors. 10,31,32 Many studies on MPNST have been limited by