Is it time to incorporate fludeoxyglucose PET/CT markers into sarcoma prediction models?

Sarcomas are relatively rare primary malignan­ cies that originate from the embryonic meso­ derm and are responsible for less than 1% of adult cancers, but comprise approximately 6% of childhood malignancies [1]. Despite aggres­ sive therapy, including surgery, adjuvant chemo­ therapy and radiotherapy, sarcoma patients’ prognosis remains guarded and overall survival has not improved substantially over the past few decades; 40% of patients with high­grade lesions will die from metastatic disease [1]. At initial histopathologic diagnosis, sarcoma grading is a fundamental step in patient evalua­ tion and plays a prominent role in overall stag­ ing. As recognized by WHO, there are two principle grading systems – the National Cancer Institute and the French Federation of Cancer Centers Sarcoma Group (FNCLCC) [2]. The more widely­used FNCLCC grade is based on three parameters: tumor differentiation, mitotic activity and necrosis. Each of these parameters receives a score: differentiation (1–3), mitotic activity (1–3) and necrosis (0–2). The sum of the scores generates a grade: grade 1 is a score of 2–3, grade 2 is 4–5 and grade 3 is 6–8. Sarcomas are extremely heterogeneous tumors, which often contain high­grade components, in addition to lower­grade areas. Frequently, sarcomas show intraturmoral necrosis, further complicating histopathological assessment. As a result of this heterogeneity, difficulty arises in accurately grading sarcomas as the assessment becomes dependent on which part of the sarcoma was biopsied and/or selected for histologic exam­ ination by the pathologist. Significant patholo­ gist interobserver variability exists when deter­ mining the histological sarcoma type, presence of necrosis and quantifying mitotic activity [3]. Given the importance of accurately determining tumor grade – and subsequently prognosis and