Medullary thyroid carcinoma: pitfalls in diagnosis by fine needle aspiration cytology and relationship of cytomorphology to RET proto-oncogene mutations

OBJECTIVE: To elucidate the pitfalls in the diagnosis of medullary thyroid carcinoma (MTC) by fine needle aspiration cytology (FNAC) and the relationship of cytomorphology to RET proto-oncogene mutations. STUDY DESIGN: Cytomorphology was reviewed in the fine needle aspiration slides of 34 patients with MTC proven by surgery and pathology. Germline or somatic RET proto-oncogene mutations were determined using polymerase chain reaction-based sequencing in 15 of 34 patients, and the relationship to cytomorphology was evaluated. RESULTS: Twenty-eight (82.4%) of 34 cases were diagnosed correctly as MTC by FNAC, 3 cases were misdiagnosed as follicular neoplasm and 1 as desmoid, and 2 cases were suspicious for MTC. The main reason for misdiagnosis was overlooking the slight angular shape of the nuclei or atypical changes. In 15 of 34 cases with germline or somatic RET proto-oncogene mutations determined, 10 cases had a germline mutation, and 1 had only a somatic mutation. There were 4 cases that had neither germline nor somatic RET proto-oncogene mutations. Cells with small/round and spindled forms were the predominant findings of codon 918 ATG-->ACG mutation, and cells with small/round and large oval to polygonal forms were the main findings of codon 634 mutations. There were no misdiagnoses in patients with RET proto-oncogene mutations. CONCLUSION: FNAC is a good diagnostic method for MTC. Codon 918 mutation correlates mainly with small/round and spindled cells and codon 634 with small/round, large oval to polygonal forms.