title: Multifocal Papillary Thyroid Cancer Increases the Risk of Central Lymph Node Metastasis.
abstract: BACKGROUND
  Papillary thyroid cancer (PTC) is the most common thyroid malignancy, with a strong predilection for lymph node metastasis, most commonly to the central neck compartment (level VI). Few studies have evaluated lymph node metastasis in multifocal PTC, and the role of level VI dissection in the management of PTC remains controversial. This retrospective analysis evaluated the rate of level VI lymph node positivity in multifocal PTC, as compared with unifocal disease, in order to inform surgical decision making better.
  
  
  METHODS
  Patients with PTC who underwent total or hemi-thyroidectomy plus level VI lymph node dissection at the authors' institution between January 2008 and June 2014 were included (N=227). The number and laterality of PTC foci, lymphovascular invasion (LVI), extrathyroidal extension (ETE), and positive/total number of level VI lymph nodes were recorded. Fisher's exact test was used to determine univariate associations, and multivariate analysis was done by logistical regression.
  
  
  RESULTS
  There was an association between the number of PTC foci and level VI node positivity (p<0.001), with an odds ratio (OR) of 2.355 in patients with three or more tumor foci (p=0.026). The OR for central neck metastasis was 1.088 with each additional focus of PTC (p=0.018). The risk of level VI node positivity in the presence of one or two foci was only 19%, with no appreciable difference between one and two foci. This risk increased in the presence of between three and nine foci (38%), and 10 or more foci (88%). Level VI node positivity was associated with ETE (p<0.001), LVI (p<0.001), and size of the largest focus (p<0.001). There was no association between level VI lymph node positivity and male sex (p=0.089), bilaterality (p=0.276), or age (p=0.076).
  
  
  CONCLUSIONS
  There is a significant association between multifocal PTC and level VI lymph node positivity, increasing proportionally with the number of foci. These findings recognize multifocality as a sign of tumor aggressiveness, as evidenced by a higher propensity for lymph node metastasis.
authors.affiliation: 1 Faculty of Medicine, Dalhousie University , Halifax, Canada .
authors.forename: Ayham
authors.initials: A
authors.lastname: Al Afif
authors.affiliation: 2 Division of Otolaryngology-Head and Neck Surgery, Dalhousie University , Halifax, Canada .
authors.forename: Blair A
authors.initials: BA
authors.lastname: Williams
authors.affiliation: 2 Division of Otolaryngology-Head and Neck Surgery, Dalhousie University , Halifax, Canada .
authors.forename: Mathew H
authors.initials: MH
authors.lastname: Rigby
authors.affiliation: 3 Department of Pathology, Dalhousie University , Halifax, Canada .
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Bullock
authors.affiliation: 2 Division of Otolaryngology-Head and Neck Surgery, Dalhousie University , Halifax, Canada .
authors.forename: S Mark
authors.initials: SM
authors.lastname: Taylor
authors.affiliation: 2 Division of Otolaryngology-Head and Neck Surgery, Dalhousie University , Halifax, Canada .
authors.forename: Jonathan
authors.initials: J
authors.lastname: Trites
authors.affiliation: 2 Division of Otolaryngology-Head and Neck Surgery, Dalhousie University , Halifax, Canada .
authors.forename: Robert D
authors.initials: RD
authors.lastname: Hart
mesh_terms: D000328:Adult; D000368:Aged; D044963:Biopsy, Fine-Needle; D002277:Carcinoma / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D002291:Carcinoma, Papillary; D003657:Decision Making; D005260:Female; D006801:Humans; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009333:Neck / Q000473:pathology; D037981:Neck Dissection; D009362:Neoplasm Metastasis; D016017:Odds Ratio; D012044:Regression Analysis; D012189:Retrospective Studies; D012307:Risk Factors; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D013965:Thyroidectomy