Familial Non Medullary Thyroid Cancer*Das familiäre, nicht medulläre Schilddrüsenkarzinom

Summary: Background: There have been an increasing number of articles regarding patients with familial non medullary thyroid cancer (FNMTC) in the past few years. FNMTC has been defined as families with two or more first degree relatives having papillary or Hurthle cell thyroid cancer. Methods: The history and new aspects of genetics, environment, pathology, management and clinical outcome of FNMTC are reviewed. Results: The familial occurrence of NFMTC was first noted in 1995. In families with three or more members with NFMTC there appears to be an autosomal dominant type of inheritance with incomplete penetrance. 99.9 % of these patients have familial disease. FNMTC without any other associated syndrome accounts for about 5 % of patients with thyroid cancer of follicular cell origin (prevalence ranges between 3.5 and 6.2 %). When two members of a family have thyroid cancer about 50 % will have a susceptibility gene for thyroid cancer. FNMTC is rare in patients with follicular thyroid cancer. To date, genetic testing to document whether an individual of a family with familial papillary or Hurthle cell cancer without other syndromes has a specific germ line mutation is not available. In 1998 a linkage site locus (thyroid cancer oxyophilia – TCO gene) on chromosome 19p13.2 in a single French family with oxyophilia and trabecular thyroid cancers was identified. Individuals with the TCO linkage site have a relatively characteristic histologic pattern with trabecular and oncocytic neoplasms. Patients with papillary thyroid cancers and familial polyposis also have a distinct architecture and primarily occur in women. An experienced pathologist can make or at least suggest that the patient with this particular histological pattern should be screened for FNMTC. When total thyroidectomy with removal of regional lymphadenopathy can be done safely this is the preferred approach for patients with nodules in families with FNMTC as recommended for patients with thyroid nodules and a history of radiation exposure. For individuals in families with two or more other members with papillary or Hurthle cell thyroid cancer and a normal thyroid gland to palpation a baseline ultrasound examination is recommended, to document whether there are any thyroid nodules present. If occult nodules are present they can be observed with a repeat ultrasound examination in six months and then yearly to be sure they are not growing, or they can be biopsied by FNA under ultrasound guidance. Although occult thyroid cancers are usually of little clinical significance this may not be true for patients with FNMTC. Occult thyroid cancers in patients with FNMTC seem more aggressive and may be lethal. Conclusions: Several groups continue to try to identify the genes responsible for the majority of families with FNMTC. Such studies are relatively expensive, but seem necessary to improve the care of patients with FNMTC.