According to 2021 ESMO Guidelines, a “high risk of metastases” can be established when any patient presents with one or more of the following criteria: (A) tumor size ≥ 5 cm; (B) any extra-adrenal PGL; (C) known SDHB germline mutation; or (D) plasma 3MT > 3 fold above the upper limit of normal [21,30]. The gene discussed is SDHB; the disease is neoplasm.