Large tumor sizes greater than 4 cm [169], high levels of Ctn, high CEA [18,100,101], high CA19.9 [53,115], high-grade tumors [115], tumors with areas of desmoplastic reaction [44,170] or lympho-vascular invasion [169], and/or RET proto-oncogene mutations increase the likelihood of distant metastasis [171]. The gene discussed is RET; the disease is neoplasm.