Lymph node metastasis in hereditary medullary thyroid cancer is independent of the underlying RET germline mutation

Although the onset of hereditary medullary thyroid cancer (MTC) depends on mutational risk, the impact of that risk on lymph node metastasis is unclear. Included in this investigation were 387 carriers of RET germline mutations with node-negative MTC (201 carriers) or node-positive MTC (186 carriers). Age at thyroidectomy increased significantly from highest (p.Met918Thr; 45 carriers), high (p.Cys634Arg/Gly/Phe/Ser/Trp/Tyr; 138 carriers) and moderate-high risk (p.Cys609/611/618/620Arg/Gly/Phe/Ser/Trp/Tyr; 93 carriers) to low-moderate risk (p.Glu768Asp, p. Leu790Phe, p. Val804Leu/Met, p. Ser891Ala; 111 carriers). In contrast, tumor progression to lymph node metastasis was similar, taking 8.6-9.1 years with moderate risk mutations and 13.6-14.5 years with high and highest risk mutations. Primary tumor size across the mutational risk spectrum changed little, measuring 18.1-22.1 mm with and 2.7-7.3 mm without lymph node metastasis. Because the biological behavior of hereditary MTC is similar after disease onset, equal treatment of comparable tumors is warranted regardless of the underlying RET mutation.