Histopathology of C Cells and Medullary Thyroid Carcinoma.

C cells are the neuroendocrine cell component of the thyroid gland that embryologically arise from the pharyngeal endoderm. Normal C cells are concentrated in the upper two-thirds of both lateral lobes, appear singly or in small groups dispersed in, among or peripherally to the follicles, and are involved in the production of calcitonin. Reactive C-cell hyperplasia should be differentiated from proliferation of atypical C cells (neoplastic C-cell hyperplasia) which is considered an intraepithelial neoplasia of C cells/medullary carcinoma in situ, a precursor lesion associated to familial medullary thyroid carcinoma (MTC). MTC typically exhibits a lobular and/or trabecular growth pattern with amyloid deposits; however, due to its great histological variability, immunohistochemical positivity for calcitonin, carcinoembryonic antigen, calcitonin-gene-related peptide, insulinoma-associated protein 1, and/or other markers is necessary to confirm diagnosis. Investigation of germline RET proto-oncogene mutation is mandatory to identify familial MTC. Somatic RET mutations or fusions as well as RAS mutations in cytological and/or biopsy samples may represent therapeutic targets. Mixed medullary and follicular-derived cell carcinoma is a heterogeneous group of tumors which needs to be distinguished from collision tumors.