The relationship between microscopic margin positivity and disease recurrence in differentiated thyroid cancer

The prognostic significance of microscopic margin positivity in well-differentiated thyroid cancer remains controversial, particularly in patients without gross residual disease. We sought to determine whether microscopic margin involvement is independently associated with locoregional recurrence or altered response to therapy in patients with T1-T2 disease.

We performed a retrospective cohort study of 502 patients with T1-T2 well-differentiated thyroid cancer who underwent total or staged thyroidectomy between 1990 and 2021 at a high-volume tertiary center. Patients with gross extrathyroidal extension or distant metastases were excluded. The primary outcome was locoregional recurrence occurring ≥12 months postoperatively. The secondary outcome was response to therapy during follow-up. Multivariable Cox and logistic regression models adjusted for age, sex, T stage, nodal status, microscopic extrathyroidal extension, and radioactive iodine therapy.

Microscopic margin positivity was identified in 67 patients (13%). Locoregional recurrence occurred more frequently in patients with positive microscopic margins compared with those with negative margins (12% vs 5%; P = .015). On multivariable analysis, microscopic margin positivity independently predicted recurrence (hazard ratio, 2.72; 95% confidence interval, 1.07-6.98). Margin status was not associated with the likelihood of achieving an excellent response to therapy (46% vs 53%; odds ratio, 0.70; 95% confidence interval, 0.38-1.29).

In patients with T1-T2 well-differentiated thyroid cancer, microscopic margin positivity is associated with an increased risk of locoregional recurrence but does not reduce the likelihood of achieving an excellent response to therapy. These findings support incorporating microscopic margin status into postoperative risk counseling and surveillance strategies rather than routine treatment escalation based solely on margin involvement.