Natural History and Predictive Factors of Outcome in Medullary Thyroid Microcarcinoma

Abstract

Context: Management of sporadic medullary thyroid microcarcinoma smaller than 1 cm (micro-MTC) is controversial because of conflicting reports of prognosis. As these cancers are often diagnosed incidentally, they pose a management challenge when deciding on further treatment and follow-up.

Objective: We report the outcomes of surgically managed sporadic micro-MTC in a specialist endocrine surgery and endocrinology unit and identify associations for recurrence and disease-specific survival in this population.

Methods: Micro-MTCs were identified from a prospectively maintained surgery database, and slides were reviewed to determine pathological grade. The primary end points were recurrence, time to recurrence and disease-specific survival. Prognostic factors assessed included size, grade, lymph node metastasis (LNM), and postoperative calcitonin.

Results: From 1995 to 2022, 64 patients were diagnosed with micro-MTC with 22 excluded because of hereditary disease. The included patients had a median age of 60 years, tumor size of 4 mm, and 28 (67%) were female. The diagnosis was incidental in 36 (86%) with 4 (10%) being high grade, 5 (12%) having LNM and 9 (21%) having elevated postoperative calcitonin. Over a 6.6-year median follow-up, 5 (12%) developed recurrence and 3 (7%) died of MTC. High grade and LNM were associated with 10-year survival estimates of 75% vs 100% for low grade and no LNM (hazard ratio = 831; P < .01). High grade, LNM, and increased calcitonin were associated with recurrence (P < .01). Tumor size and type of surgery were not statistically significantly associated with recurrence or survival. No patients with low grade micro-MTC and normal postoperative calcitonin developed recurrence.

Conclusion: Most sporadic micro-MTCs are detected incidentally and are generally associated with good outcomes. Size is not significantly associated with outcomes. Using grade, LNM, and postoperative calcitonin allows for the identification of patients at risk of recurrence to personalize management.

Keywords: medullary thyroid cancer; medullary thyroid microcarcinoma; outcomes; surgery; tumor grade.

Figure 1.

Representative image of low-grade medullary thyroid microcarcinoma, A, serial hematoxylin and eosin (H&E), and B, Ki67 immunohistochemistry H&E-stained section from a 2-mm tumor. The tumor has a mitotic count of less than 1 per 2 mm², a Ki67 proliferative index of less than 1%, and lacks tumor necrosis. Therefore, under the grading system the tumor is low grade (original magnification 200×).

Figure 2.

Patient flowchart. MEN, multiple endocrine neoplasia; MTC, medullary thyroid carcinoma.

Figure 3.

Kaplan-Meier curves comparing patients with medullary thyroid microcarcinoma on the basis of A, time to recurrence (TTR) for tumor size (< 5 mm/5-10 mm); B, TTR for tumor grade (low/high); C, TTR for lymph node involvement (negative/positive); and D, TTR for postoperative calcitonin (normal/increased).

Figure 4.

Kaplan-Meier curve comparing patients with medullary thyroid microcarcinoma on the basis of A, disease-specific survival (DSS) for tumor size (< 5 mm/5 to 10 mm); B, DSS for tumor grade (low/high); C, DSS for lymph node involvement (negative/positive); and D, DSS for postoperative calcitonin (normal/increased).