Forgoing node dissection for desmoplasia-negative hereditary medullary thyroid cancer

Clinically inapparent node metastases, requiring neck dissection in addition to thyroidectomy, pose a diagnostic challenge in patients with medullary thyroid cancer (MTC). Although desmoplasia negativity has emerged as a powerful marker of node-negative disease, its clinical utility in hereditary MTC remains ill-defined. This cross-sectional investigation employed multivariable logistic regression on, and stratification of clinical variables by, nodal status of 124 RET carriers with MTC who underwent initial total thyroidectomy with at least central neck dissection between 2000 and 2025 at a tertiary center. Unlike tumor size, grade, laterality, index status, and sex, only desmoplasia (>10% vs ≤5%), basal serum calcitonin (>500 pg/mL >> 101-500 pg/mL vs ≤100 pg/mL), and RET category (highest (p.Met918Thr) vs any other) were independently associated with node metastases. In unilateral MTC, desmoplasia ≤5% was always associated with freedom from node metastases (0 of 15 patients), whereas tumor size ≤5 mm and basal serum calcitonin ≤100 pg/mL were associated with node metastases in 4 (18%) of 22 patients and 4 (15%) of 26 patients, respectively. In bilateral MTC, none of the above thresholds were sufficiently discriminatory, suggesting metastatic cross-contamination by the contralateral MTC. In unilateral MTC with desmoplasia ≤5%, node metastases were always absent, regardless of whether basal calcitonin levels were ≤100 (based on 13 patients) or >100 pg/mL (based on 2 patients). This comprehensive proof-of-concept study demonstrates that RET carriers with desmoplasia-negative unilateral MTC may forgo node dissection at specialist centers, similarly to what has been proposed for patients with desmoplasia-negative sporadic MTC.