Familial follicular cell-derived well-differentiated
thyroid cancer, papillary (PTC), and
follicular thyroid carcinomas (
FTC), accounts for 95% of thyroid
malignancies. The majority of are sporadic, and at least 5% of these patients will have familial disease. Familial thyroid syndromes are classified into
familial medullary thyroid carcinoma (FMTC), derived from
calcitonin-producing C cells, and familial follicular cell
tumors or non-medullary
thyroid carcinoma (FNMTC), derived from follicular cells. Twenty-five percent of patients with
medullary thyroid cancer (MTC) have a familial form; however, this accounts for only 1% of all patients with
thyroid cancer. The familial follicular cell-derived lesions or familial non-
medullary thyroid cancer can be divided into two clinical-pathological groups. The first group includes familial syndromes characterized by a predominance of non-thyroidal
tumors, such as
familial adenomatous polyposis (FAP),
PTEN-hamartoma tumor syndrome (
Cowden disease; PHTS),
Carney complex,
Werner syndrome, and
Pendred syndrome. The second group includes familial syndromes characterized by predominance of
papillary thyroid carcinoma (PTC), such as pure fPTC, fPTC associated with
papillary renal cell carcinoma, and fPTC with multinodular
goiter. Most of the progress in the genetics of familial
thyroid cancer has been in patients with MTC. This is usually a component of multiple endocrine
neoplasias IIA or IIB, or as pure
familial medullary thyroid carcinoma syndrome. The genetic events in the familial C-cell-derived
tumors are known and genotype-phenotype correlations are well established. The mutations in patients with isolated NMFTC have not been as well defined as in MTC. In many cases, patients have a known familial syndrome that has defined risk for
thyroid cancer. The clinician must be knowledgeable in recognizing the possibility of an underlying familial syndrome when a patient presents with
thyroid cancer. Some characteristic thyroid morphologic findings should alert the pathologist of a possible familial
cancer syndrome, which may lead to further molecular genetics evaluation.