Natural History and Predictive Factors of Outcome in Medullary Thyroid Microcarcinoma

J Clin Endocrinol Metab. 2023 Mar 25;dgad173. doi: 10.1210/clinem/dgad173. Online ahead of print.


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

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

Results: From 1995-2022, 64 patients were diagnosed with micro-MTC with 22 excluded due to hereditary disease. The included patients had a median age of 60, tumour 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 post-operative calcitonin. Over a 6.6-year median follow up, 5 (12%) developed recurrence and 3 (7%) died from MTC. High grade and LNM was associated with 10-year survival estimates of 75% versus 100% for low grade and no LNM (HR = 831, P < 0.01). High grade, LNM and raised calcitonin were associated with recurrence (P < 0.01). Tumour size and type of surgery were not significantly associated with recurrence or survival. No patients with low grade micro-MTC and normal post-operative calcitonin developed recurrence.

Conclusions: Most sporadic micro-MTC are detected incidentally and are generally associated with good outcomes. Size is not significantly associated with outcomes. Utilising grade, LNM and post-operative calcitonin allows for identification of patients at risk of recurrence to personalise management.

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