Summary

This paper updates the histopathology and cytopathology of thyroid tumors and proliferations derived from the para-follicular or C cells. Beginning with an historical over view, including the recognition of medullary thyroid carcinoma as a distinct histologic entity, its relationship to the hormone, calcitonin, (which was discovered in the same decade) and to thyroid C cells, medullary carcinoma and its variants are reviewed. The molecular biology of the tumors and the associated mutations in the tumors (somatic mutations) are discussed. Additionally the genetic features (germline mutations) including familial clusters and associations with other endocrine and neuroendocrine lesions are reviewed. Screening for the tumor and its precursors is included with a review of the latest American Thyroid Association guidelines for treatment as well as timing and approach to surgery. Tabular data of specific germline mutations and their relationships to tumor virulence, and prognosis are illustrated. Precursor and early C cell lesions such as C-cell hyperplasia and micro-medullary carcinoma are discussed. Difficulties and controversies in the definition of C-cell proliferations which are neoplastic and those which are “reactive” are reviewed. The entity of medullary microcarcinoma or medullary microcarcinoma is illustrated and the distinction between C cell nodules and microcarcinoma is defined using the latest available criteria. Finally the latest approved chemotherapeutic agents and their results in metastatic medullary thyroid carcinoma are included.