Multifocality in sporadic medullary thyroid carcinoma is associated with low tumor grade and no difference in somatic driver mutations or overall survival when compared with unifocal tumors

Background: Total thyroidectomy for patients with sporadic medullary thyroid carcinoma is often recommended because of multifocality. The International Medullary Thyroid Carcinoma Grading System is established as a predictor of disease-specific outcomes. We aimed to study multifocality and its association with index tumor grade and somatic mutations. Methods: A retrospective cohort analysis of 5 high-volume medullary thyroid carcinoma centers was performed between January 1, 1986, and January 1, 2018. Thyroidectomy specimens were evaluated for multifocality. Molecular profiling was assessed with RET germline testing and/or targeted exome sequencing of specimens with matched normal DNA. Outcomes evaluated were risk of local recurrence, distant recurrence, and survival within 15 years. Results: Among 270 patients with nongermline medullary thyroid carcinoma, 207 (77%) were unifocal and 63 (23%) multifocal (P < .05). A similar proportion of patients were low-grade (unifocal: 75% vs multifocal: 79%; P = .45) although a significantly greater proportion of multifocal patients demonstrated C-cell hyperplasia (48% vs 9%; P < .001). Molecular profiling identified no differences among driver mutations. The median size of multifocal lesions was 0.60 cm (interquartile range: 0.3—1.0 cm) with 74% harboring multiple foci. The ratio of positive lymph nodes in dissected compartments was similar (multifocal: 0.37, interquartile range: 0—0.66 vs unifocal: 0.27, interquartile range: 0—0.43; P = .23). Local recurrence (P = .25) and overall survival (P = .31) were not statistically different between cohorts. Conclusion: Subcentimeter multifocality is common in sporadic medullary thyroid carcinoma. In this study cohort, no differences were observed in tumor grade, lymph node burden, overall survival, or somatic driver mutations compared with unifocal tumors. Multifocality in patients with sporadic medullary thyroid carcinoma is not associated with adverse overall survival.