Mixed medullary-papillary carcinoma of the thyroid: a previously unrecognized variant of thyroid carcinoma.

Two unusual medullary carcinomas of the thyroid gland and their metastases contained a population of cells (20% to 25%) with the characteristic clear nuclei of papillary carcinoma. The predominant component of the tumors exhibited the typical growth pattern and cytologic features of medullary carcinoma with abundant amyloid deposits. The cells with clear nuclei lined follicle-like or tubular structures. In both the primary and the metastatic lesions, immunoreactive thyroglobulin was demonstrated only in the cells with clear nuclei, while calcitonin, carcinoembryonic antigen, and neuron-specific enolase were present only in cells of the predominant medullary carcinomatous component. Moreover, intense and diffuse staining for cytokeratin was seen only in the cells with clear nuclei, but not in those of the major medullary carcinomatous component. These findings suggest the existence of a distinctive variant of mixed medullary-papillary carcinoma that can be recognized with routine stains.