Familial Papillary Thyroid Carcinoma: Genetics, Criteria for Diagnosis, Clinical Features, and Surgical Treatment

Abstract

Hereditable predisposition to papillary thyroid carcinoma (PTC) and multinodular goiter (MNG) without evidence of an association with other malignancies as a distinct entity was recognized only recently. A meta-review of the literature on familial PTC (FPTC) was undertaken, and characteristics of families with frequent occurrence of PTC or MNG (or both) were summarized. A database on thyroid cancer patients maintained in our institution was searched 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 histopathologic features of the FPTC cases were compiled. Based on the FPTC meta-review and own experience, predictive criteria to identify families at risk were developed: Exclusion criteria were previous radiation exposure and coincidence 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 criteria 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 predisposition to PTC is considered if both primary criteria or one primary criterion plus three secondary criteria are present. Family history-taking is recommended 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 intervention.

Familial thyroid cancer: a review

“…Tumor-specific loss of heterozygosity is found in sporadic FTC with and without oxyphilia at both 19p13 and 2q21.32. 27,63,64 FNMTC type 1 syndrome The FNMTC type 1 syndrome (chromosomal region 2q21) is characterized by PTC without any distinguishing pathologic features and without an obvious increase in frequency of non-thyroidal neoplasms in kindred members. 70 fPTC associated with renal papillary neoplasia The fPTC associated with renal papillary neoplasia presents with the usual classical variant of PTC and with no special features.…”

“…Statistical estimates suggest that a grouping of two family members with NMTC could represent the concurrence of sporadic tumors, but thyroid tumors in three or more members in kindred, or the diagnosis of PTC in men and children, is more suggestive of a familial predisposition. [24][25][26][27][28][29][30][31][32][33][34][35][36][37]61 Although non-medullary thyroid cancer is mostly sporadic, evidence for a familial form, not associated with other Mendelian cancer syndromes described above (eg FAP and CS), is well documented and thought to cause more aggressive disease. The search for a genetic susceptibility locus for FNMTC started about a decade ago.…”

“…FNMTC patients have shorter disease-free survival than do sporadic disease patients because of frequent locoregional recurrence. [24][25][26][27][28][29][30][31][32][33][34][35][36][37]61 The genetic inheritance of FNMTC remains unknown, but it is believed to be an autosomal dominant mode with incomplete penetrance and variable expressivity. Genetic analyses of large FNMTC kindreds not only support the hypothesis of an inherited genetic predisposition to FNMTC, but also represent the first steps in identification of the putative susceptibility genes.…”

Familial vs sporadic papillary thyroid carcinoma: a matched-case comparative study showing similar clinical/prognostic behaviour

“…A vast majority of patients with FNMTC present papillary thyroid carcinoma (PTC), although benign thyroid lesions, such as multinodular goitre, are also commonly found in members of these families (2,4,5).…”

Carcinoma não medular familiar da tiróide

“…O tipo histológico mais comum é o papilífero, sendo o carcinoma de células de Hürthle e o carcinoma folicular os mais raros. O carcinoma papilífero familiar está associado a maior incidência de condições benignas tiroideanas (adenoma folicular, bócio multinodular e tiroidite) (11). Como na forma esporádica, as mulheres são 2 a 3 vezes mais afetadas que os homens, porém com início de doença numa faixa etária um pouco mais jovem.…”