Familial differentiated carcinoma of the thyroid

Abstract

In most series, thyroid cancers arising from follicular cells account for about 90% of malignant tumors of the thyroid [1-3]. The remainder are medullary cancers, which arise from parafollicular cells, lymphomas, sarcomas, and metastatic cancers. A proportion of medullary cancers are unequivocally recognized to be hereditary. These include medullary cancers occurring as part of the syndromes of multiple endocrine neoplastic syndromes MEN 2A and MEN 2B (MEN 3) and some isolated cases of medullary cancer [4]. These are discussed separately in Chap. 20. The genetics have been defined as autosomal dominant, and the cause of MEN 2A and familial medullary cancer is a mutation in the cret proto-oncogene [5-8]. Differentiated or nonmedullary cancers of the follicular epithelium are usually considered to be sporadic and nonfamilial. There is a growing body of evidence that some cases are familial. In my clinic about 2% of patients have a first-degree relative with similar disease. Some report an incidence of 4-5% [9, 10]. The first report was in identical twins and was published in 1955 [11]. There are now several reports of familial cases, including several from this institute [12-29]. Some investigators consider that familial thyroid cancers are more aggressive than the sporadic cases [9, 30]. This chapter will review the published reports and as far as possible analyze whether the natural history of the disease is different from the sporadic variety. The mode of inheritance and genetic susceptibility, including the relationship with Cowden's, Gardner's, and other syndromes are discussed. The molecular genetics will be reviewed. Advice about management of the patients and their families is included. © Springer-Verlag Berlin Heidelberg 2001, 2005.