High-grade medullary thyroid carcinoma with papillary-like nuclear features: A report of five cases

Background Medullary thyroid carcinoma (MTC) with papillary-like nuclear features has not been previously described. Here, we aimed to describe the unique features of MTC and examine their prognostic value as markers of high-grade MTC.Methods Of the 110 MTC patients reviewed, a total of five (4.5%) who exhibited MTC with papillary-like nuclear features based on observations from cytological preparations were included in this study. Papillary-like nuclear features were defined as exhibiting all of the following characteristics: ground-glass chromatin pattern, grooves, indented membrane, and lobulation.Results The patients included four females and one male, with a median age of 70 years. Calcitonin-doubling times for patients 1 and 3 were 0.8 and 0.34 years, respectively. Cytologically, patients 4 and 5 displayed a Ki-67 labeling index of 5.1% and necrotic cells, respectively. All three histologically evaluated patients exhibited papillary-like nuclear features and a Ki-67 labeling index of >5.0%. Patients 1 and 3 had mitotic counts of >=;5 per 2 mm(2). The MTC in all five patients was classified as high-grade. Moreover, patient 1 harbored a RET mutation (M918T), while RET (R912W), BRAF (V600E), and CTNNB1 (S33F, T41I) mutations were present in patient 2.Conclusion Our work suggests that papillary-like nuclear features in MTC may be associated with high-grade tumors. These findings may be cytologically indicative of high-grade tumors other than necrosis or mitosis.