title: 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.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Section of Endocrine Surgery, Department of Surgery, University of Wisconsin, Madison, Wisconsin 53792, USA.
authors.forename: Haggi
authors.initials: H
authors.lastname: Mazeh
authors.forename: Joy
authors.initials: J
authors.lastname: Benavidez
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Poehls
authors.forename: Linda
authors.initials: L
authors.lastname: Youngwirth
authors.forename: Herbert
authors.initials: H
authors.lastname: Chen
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Sippel
mesh_terms: D018263:Adenocarcinoma, Follicular; D018249:Adenoma, Oxyphilic; D000328:Adult; D002277:Carcinoma; D002291:Carcinoma, Papillary; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D012189:Retrospective Studies; D012720:Severity of Illness Index; D000077273:Thyroid Cancer, Papillary; D065646:Thyroid Carcinoma, Anaplastic; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D013965:Thyroidectomy