Familial papillary thyroid carcinoma: Genetics, criteria for diagnosis, clinical features, and surgical treatment

Hereditable predisposition to papillary thyroid carcinoma (PTC) and multino dular goiter (MNG) without evidence of an association with other malignanci es as a distinct entity was recognized only recently. A meta-review of the literature on familial PTC (FPTC) was undertaken, and characteristics of fa milies with frequent occurrence of PTC or MNG (or both) were summarized. A database on thyroid cancer patients maintained in our institution was searc hed for potential FPTC families. Clinical examinations were performed in 6 of 12 Hannover kindreds identified, and blood samples of all family members were collected for genetic analyses. Clinical presentations and histopatho logic features of the FPTC cases were compiled. Based on the FPTC meta-revi ew and own experience, predictive criteria to identify families at risk wer e developed: Exclusion criteria were previous radiation exposure and coinci dence with neoplasia syndromes. Primary criteria for susceptibility to FPTC are (1) PTC in two or more first-degree relatives and (2) MNG in at least three first- or second-degree relatives of a PTC patient. Secondary criteri a are diagnosis in a patient younger than 33 years, multifocal or bilateral PTC, organ-exceeding tumor growth (T4), metastasis (N1, M1), and familial accumulation of adolescent-onset thyroid disease. A hereditary predispositi on to PTC is considered if both primary criteria or one primary criterion p lus three secondary criteria are present. Family history-taking is recommen ded for all PTC patients to identify FPTC kindreds at risk. Blood relatives of FPTC index patients who harbor MNG should undergo thorough and regular clinical screening. Suspicious lesions should prompt early surgical interve ntion.