C-Cell Lesions and Medullary Thyroid Carcinoma: A Review.

Advances in genetic studies, tumor grading, and targeted therapy have improved diagnosis and management of medullary thyroid carcinoma (MTC). This rare neuroendocrine neoplasm is linked to hereditary MEN2 syndromes driven by germline RET mutations, while sporadic tumors frequently harbor somatic RET or RAS alterations. The disease develops from proliferation of neoplastic C-cells. Histologically, MTC often demonstrates diverse morphologies; classic MTC features include nests of neuroendocrine cells associated with stromal amyloid. Immunohistochemical expression of calcitonin, CEA, chromogranin, and synaptophysin aid in diagnosis. Recently established grading criteria based on mitotic activity, Ki-67 proliferation index, and tumor necrosis have improved prognostic evaluation and risk stratification. Genetic sequencing and selective RET inhibitors have also enhanced precision-based management and outcomes in advanced RET-mutated tumors.