Familial Follicular Cell Tumors: Classification and Morphological Characteristics

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.