C-cell hyperplasia. An ultrastructural analysis.

The C-cell is the source of the hypocalcemic polypeptide hormone, calcitonin. Sequential increments in calcitonin response to provocative calcium and pentagastrin infusions have been used to identify family members at high risk for the development of medullary thyroid carcinoma, a neoplasm of C-cell origin. Correlative light microscopic and immunohistochemical studies have permitted the identification of a spectrum of C-cell proliferative abnormalities ranging from C-cell hyperplasia (CCH) to invasive medullary thyroid carcinoma. Ultrastructurally, both normal and hyperplastic C-cells occupied an intrafolliculat localization, being separated from the interstitium by the follicular basal lamina and from the luminal colloid by extensions of the follicular cell cytoplasm. These relationships were maintained in areas of advanced hyperplasia where C-cells often completely encircled and displaced the follicular epithelium. Nodular CCH was characterized by the complete obliteration of the follicular space by C-cells. In these areas, prominent reduplications as well as occasional defects in the basal lamina were noted. Some of the solid C-cell nodules adjacent to areas of medullary thyroid carcinoma appeared to form by gradual replacement of follicles by C-cells and did not represent sites of intrathyroidal vascular or lymphatic extension. Two major cell types were noted in cases of CCH. One cell type which was filled with secretory granules measureing 280 nm. in diameter (type I) predominated in areas of diffuse CCH and was also found in control thyroid glands. The larger number of secretory granules in this cell type together with the relative lack of development of granular endoplasmic reticulum and Golgi regions suggested that these cells were in the storage phase of their secretory cycle. The second cell type had fewer secretory granules, which measured 130 nm. in diameter (type II), and was characteristically located in areas of nodular CCH. Type II granules were found in cells with cytologic evidence of active protein synthesis and secretion. Variations in granule morphology and cell ultrastructure may be correlated with functional variations in C-cell populations.