In Patients with Thyroid Cancer of Follicular Cell Origin, a Family History of Nonmedullary Thyroid Cancer in One First-Degree Relative Is Associated with More Aggressive Disease

Section of Endocrine Surgery, Department of Surgery, University of Wisconsin, Madison, Wisconsin 53792, USA.
Thyroid: official journal of the American Thyroid Association (Impact Factor: 4.49). 12/2011; 22(1):3-8. DOI: 10.1089/thy.2011.0192
Source: PubMed


About 5% of nonmedullary thyroid cancers (NMTCs) are familial. Most patients with a family history of thyroid cancer do not meet the definition of familial NMTC (FNMTC; two or more affected family members). The aim of this study was to determine whether patients with a family history of NMTC, but who do not meet the definition of FNMTC, have more aggressive disease.
A database of 1502 thyroidectomies was reviewed and 358 patients with NMTC who did not have a family history of benign thyroid disease and who underwent thyroidectomy from January 1994 to December 2008 were identified. These included 324 (90%) patients with papillary thyroid carcinoma (PTC), 24 (7%) with follicular thyroid cancer, and 10 (3%) with anaplastic or Hürthle cell carcinoma. Among them, those with and without a family history of NMTC in first-degree relatives were compared. Then patients with only one affected family member were compared with FNMTC patients.
Thirty-seven (10%) patients had a family history of thyroid cancer, all to of which had PTC. Patients with a family history of NMTC had a similar tumor size than those without (2±0 vs. 2.1±0 cm, p=0.72) but they were significantly younger (43±3 vs. 49±1 years, p=0.04), and more likely to have multicentricity (48% vs. 22%, p=0.01), malignant lymph nodes (22% vs. 11%, p=0.02), and local invasion to surrounding tissues (5.4% vs. 0.6%, p=0.007). They also had a higher recurrence rate (24% vs. 12%, p=0.03) than patients without a family history. Interestingly, patients with only one affected family member were similar to FNMTC patients with respect to age (44±4 vs. 40±3 years, p=0.4), tumor size (2±0 vs. 1.9±0 cm, p=0.65), rate of multicentricity (44% vs. 52%, p=0.57), malignant lymph nodes (22% vs. 21%, p=0.93), local invasiveness (5.5% vs. 11%, p=0.59), and disease recurrence (28% vs. 21%, p=0.56).
Patients with NMTC having a family history of thyroid cancer have more aggressive disease, regardless of whether they meet the current definition of FNMTC regarding number of affected family members. Therefore, any positive family history should be considered a risk factor for more aggressive thyroid carcinoma.

Download full-text


Available from: Haggi Mazeh
  • Source
    • "have familial origins, whereby an individual's risk of developing thyroid cancer is >95% if there are three or more affected family members [2]. Whether from a familial origin or sporadic, these types of thyroid cancers are histologically indistinguishable [2]. Well-differentiated cancers typically have an excellent prognosis, with cure rates greater than 90% when treated surgically with or without postoperative radioiodine [5]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Thyroid cancer is an endocrine malignancy with an incidence rate that has been increasing steadily over the past 30 years. While well-differentiated subtypes have a favorable prognosis when treated with surgical resection and radioiodine, undifferentiated subtypes, such as anaplastic thyroid cancer (ATC), are far more aggressive and have a poor prognosis. Conventional therapies (surgical resection, radiation, chemotherapy, and radioiodine) have been utilized for treatment of ATC, yet these treatments have not significantly improved the overall mortality rate. As cancer is a genetic disease, genetic alterations such as mutations, fusions, activation of oncogenes, and silencing of tumor suppressors contribute to its aggressiveness. With the use of next-generation sequencing and the Cancer Genome Atlas, mutation-directed therapy is recognized as the upcoming standard of care. In this review, we highlight the known genetic landscape of ATC and the need for a comprehensive genetic characterization of this disease in order to identify additional therapeutic targets to improve patient outcomes.
    Full-text · Article · Sep 2014 · Journal of Oncology
  • Source
    • "Individuals with FNMTC have an increased risk of multifocal disease, local invasion, and increased local or regional recurrence, lymph node metastases, and intraglandular dissemination. FNMTC is an independent predictor of shorter disease-free survival (Malchoff et al., 1999; Alsanea et al., 2000; Musholt et al., 2000; Alsanea and Clark, 2001; Hemminki et al., 2005; Sturgeon and Clark, 2005; Charkes, 2006; Mazeh et al., 2012). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Follicular cell-derived well-differentiated thyroid cancer, papillary (PTC) and follicular thyroid carcinomas comprise 95% of all thyroid malignancies. Familial follicular cell-derived well-differentiated thyroid cancers contribute 5% of cases. Such familial follicular cell-derived carcinomas or non-medullary thyroid carcinomas (NMTC) are divided into two clinical-pathological groups. The syndromic-associated group is composed of predominately non-thyroidal tumors and includes Pendred syndrome, Warner syndrome, Carney complex (CNC) type 1, PTEN-hamartoma tumor syndrome (PHTS; Cowden disease), and familial adenomatous polyposis (FAP)/Gardner syndrome. Other conditions with less established links to the development of follicular cell-derived tumors include ataxia-telangiectasia syndrome, McCune Albright syndrome, and Peutz-Jeghers syndrome. The final group encompasses syndromes typified by NMTC, as well as pure familial (f) PTC with or without oxyphilia, fPTC with multinodular goiter, and fPTC with papillary renal cell carcinoma. This heterogeneous group of diseases does not have the established genotype-phenotype correlations known as in the familial C-cell-derived tumors or medullary thyroid carcinomas (MTC). Clinicians should have the knowledge to identify the likelihood of a patient presenting with thyroid cancer having an additional underlying familial syndrome stemming from characteristics by examining morphological findings that would alert pathologists to recommend that patients undergo molecular genetic evaluation. This review discusses the clinical and pathological findings of patients with familial PTC, such as FAP, CNC, Werner syndrome, and Pendred syndrome, and the heterogeneous group of familial PTC.
    Full-text · Article · May 2012 · Frontiers in Endocrinology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Although hereditary nonmedullary thyroid cancer is recognized as a distinct and isolated familial syndrome, the precise prevalence and genetic basis are poorly understood. Moreover, whether familial nonmedullary thyroid cancer (FNMTC) has a more aggressive clinical behavior is controversial. The objectives of this study were to determine the prevalence of FNMTC, and compare the extent of disease and tumor somatic genetic alteration in patients with familial and sporadic papillary thyroid cancer. Methods: The main study entry criterion was patients who had a thyroid nodule that required a clinical evaluation with fine-needle aspiration biopsy and or thyroidectomy. A family history questionnaire was used to determine the presence of familial and sporadic thyroid cancer. Thyroid nodule fine-needle aspiration biopsy samples and tumor tissue at the time of thyroidectomy were used to test for somatic genetic mutations (BRAF V600E, NRAS, KRAS, NTRK1, RET/PTC1, and RET/PTC3). Results: There were 402 patients with 509 thyroid nodules enrolled in the study. The prevalence of FNMTC was 8.8% in all patients with thyroid cancer and 9.4% in patients with only papillary thyroid cancer. None of the patients with FNMTC had another familial cancer syndrome. There was no significant difference in gender, tumor size, lymph node metastasis, and overall stage between sporadic and familial cases of thyroid cancer. Patients with FNMTC were younger at diagnosis than patients with sporadic papillary thyroid cancer (p < 0.002). Seventy-nine of the 504 thyroid nodules had somatic genetic mutations (29 BRAF V600E, 29 NRAS, 8 KRAS, 1 NTRK1, 4 RET/PTC1, and 8 RET/PTC3). There was no significant difference in the number or type of somatic mutations between sporadic and hereditary cases of papillary thyroid cancer. Conclusions: We found a higher prevalence of FNMTC in patients with papillary thyroid cancer than previously reported. Patients with FNMTC present at a younger age. Somatic mutations and extent of disease are similar in sporadic and FNMTC cases.
    Preview · Article · Dec 2010 · Thyroid: official journal of the American Thyroid Association
Show more