Dissection of RET p.M918T-driven progression of hereditary vs. sporadic medullary thyroid cancer

Abstract

Background

Whether inherited in the context of multiple endocrine neoplasia 2B at germline level or acquired in a lifetime, all RET p.M918T (RET c.2753T>C) mutations should activate the RET tyrosine kinase receptor alike, with similar degrees of medullary thyroid cancer (MTC) progression when disparities in disease onset and multifocal growth are accounted for.

Methods

This cross-sectional analysis of RET p.M918T-driven progression of hereditary MTC (33 patients) vs. sporadic MTC (36 patients) sought to explore this hypothesis.

Results

Patients with hereditary disease were significantly younger at thyroidectomy (medians of 10 vs. 57 yrs.) and featured significantly more often multifocal growth (69 vs. 14 %) with more thyroid tumor foci (medians of 2 foci vs. 1 focus) than patients with sporadic disease.

Although the former had 3.6-fold smaller primary thyroid tumor diameters (medians of 5 vs. 18 mm) and twice as many neck nodes dissected (medians of 66.5 vs. 32 nodes) than the latter, extrathyroid tumor extension (42 vs. 36 %), node metastasis (64 vs. 77 %), distant metastasis (33 vs. 17 %), and biochemical cure rates (45 vs. 35 %) were fairly comparable, as was the number of dissected node metastases (medians of 7 vs. 8 involved nodes).

Sensitivity analyses, with breakdown of patients by tumor multifocality and nodal status, corroborated these findings.

Conclusion

RET p.M918T-driven progression of MTC is similar in hereditary and sporadic disease, barring earlier development and more frequent multifocal growth of hereditary MTC. This makes a compelling case for referral of patients with RET p.M918T-driven MTCs to specialist surgical centers.