A Case of Concurrent Papillary Thyroid Carcinoma in Familial Medullary Thyroid Microcarcinoma with a Germline C634W Mutation

ABSTRACT

The origins of medullary carcinoma (MTC) and papillary carcinoma (PTC) of the thyroid are embryologically different. Tumors showing concurrent medullary and papillary features are rare and they represent less than 1% of all thyroid malignancies. Hereditary MTC is an autosomal dominantly inherited disease which is genetically determined as part of the MEN 2A, MEN 2B, or variants of MEN 2A such as familial MTC. Germline mutations of the RET gene are the underlying cause of the majority of cases of hereditary medullary carcinomas. The pathogenesis of concurrent PTC with familial MTC has rarely been known. Genetic analysis of the RET oncogene has so far provided conflicting results. Here we describe a family whose sibling was affected by both PTC & MTC, and the family carried a germ-line point mutation in the RET extracellular domain that converted cysteine 634 into tryptophan (C634W).