title: Bethesda Categorization of Thyroid Nodule Cytology and Prediction of Thyroid Cancer Type and Prognosis.
abstract: BACKGROUND
  Since its inception, the Bethesda System for Reporting Thyroid Cytopathology (TBS) has been widely adopted. Each category conveys a risk of malignancy and recommended next steps, though it is unclear if each category also predicts the type and extent of malignancy. If so, this would greatly expand the utility of the TBS by providing prognostic information in addition to baseline cancer risk.
  
  
  METHODS
  All patients prospectively enrolled into the authors' thyroid nodule database from 1995 to 2013 with histologically proven malignancy were analyzed. The primary ultrasound-guided fine-needle aspiration cytology (AUS, atypia of unknown significance; FN, follicular neoplasm; SUSP, suspicious; M, malignant) was correlated with the type of thyroid cancer and histological features known to impact prognosis and recurrence, including lymph node metastasis (LNM), lymphovascular invasion, and extrathyroidal extension (ETE). Primary cytology was separately correlated with higher risk malignancy.
  
  
  RESULTS
  A total of 1291 malignancies were identified, with primary cytology AUS in 130 cases, FN in 241 cases, SUSP in 411 cases, and M in 509 cases. AUS, SUSP, and M cytology were progressively associated with an increasing risk of high-risk disease (p < 0.001), LNM (p < 0.001), ETE (p < 0.001), and margin positivity (p < 0.001). Notably, 71% of malignancies with AUS cytology were follicular variants of papillary thyroid cancer compared with 63% with SUSP cytology and only 20% with M cytology. In contrast, high-risk malignancies were diagnosed in only 4% with AUS cytology, but 9% and 27% with SUSP and M cytology, respectively. FN conveyed a significantly increased risk of follicular thyroid carcinoma compared with all other types (28% vs. 2%; p < 0.001). A composite endpoint of recurrence, distant metastases, and death similarly increased as cytology progressed from AUS to SUSP to M (p < 0.001).
  
  
  CONCLUSIONS
  In addition to predicting cancer prevalence, the TBS also imparts important prognostic information about cancer type, variant, and risk of recurrence. These data extend the utility of TBS classification by fostering an improved understanding of the risk posed by any confirmed malignancy.
authors.affiliation: 1 Thyroid Unit, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School , Boston, Massachusetts.|2 Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University , Nanjing, China .
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Liu
authors.affiliation: 3 Rotterdam Thyroid Center and Department of Internal Medicine, Erasmus Medical Center , Rotterdam, the Netherlands .
authors.forename: Marco
authors.initials: M
authors.lastname: Medici
authors.affiliation: 1 Thyroid Unit, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School , Boston, Massachusetts.
authors.forename: Norra
authors.initials: N
authors.lastname: Kwong
authors.affiliation: 1 Thyroid Unit, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School , Boston, Massachusetts.
authors.forename: Trevor E
authors.initials: TE
authors.lastname: Angell
authors.affiliation: 1 Thyroid Unit, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School , Boston, Massachusetts.
authors.forename: Ellen
authors.initials: E
authors.lastname: Marqusee
authors.affiliation: 1 Thyroid Unit, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School , Boston, Massachusetts.
authors.forename: Matthew I
authors.initials: MI
authors.lastname: Kim
authors.affiliation: 1 Thyroid Unit, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School , Boston, Massachusetts.
authors.forename: P Reed
authors.initials: PR
authors.lastname: Larsen
authors.affiliation: 4 Department of Surgery, Brigham and Women's Hospital and Harvard Medical School , Boston, Massachusetts.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Cho
authors.affiliation: 4 Department of Surgery, Brigham and Women's Hospital and Harvard Medical School , Boston, Massachusetts.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Nehs
authors.affiliation: 4 Department of Surgery, Brigham and Women's Hospital and Harvard Medical School , Boston, Massachusetts.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Ruan
authors.affiliation: 4 Department of Surgery, Brigham and Women's Hospital and Harvard Medical School , Boston, Massachusetts.
authors.forename: Atul
authors.initials: A
authors.lastname: Gawande
authors.affiliation: 4 Department of Surgery, Brigham and Women's Hospital and Harvard Medical School , Boston, Massachusetts.
authors.forename: Francis
authors.initials: F
authors.lastname: Moore
authors.affiliation: 5 Department of Pathology, Brigham and Women's Hospital and Harvard Medical School , Boston, Massachusetts.
authors.forename: Justine
authors.initials: J
authors.lastname: Barletta
authors.affiliation: 5 Department of Pathology, Brigham and Women's Hospital and Harvard Medical School , Boston, Massachusetts.
authors.forename: Jeffrey F
authors.initials: JF
authors.lastname: Krane
authors.affiliation: 5 Department of Pathology, Brigham and Women's Hospital and Harvard Medical School , Boston, Massachusetts.
authors.forename: Edmund S
authors.initials: ES
authors.lastname: Cibas
authors.affiliation: 2 Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University , Nanjing, China .
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.affiliation: 1 Thyroid Unit, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School , Boston, Massachusetts.
authors.forename: Erik K
authors.initials: EK
authors.lastname: Alexander
mesh_terms: D000328:Adult; D044963:Biopsy, Fine-Needle; D002277:Carcinoma / Q000145:classification / Q000175:diagnosis* / Q000473:pathology*; D002291:Carcinoma, Papillary; D003581:Cytodiagnosis / Q000379:methods*; D016208:Databases, Factual; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D011446:Prospective Studies; D012306:Risk; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000145:classification / Q000175:diagnosis* / Q000473:pathology*; D016606:Thyroid Nodule / Q000145:classification / Q000175:diagnosis* / Q000473:pathology*; D014463:Ultrasonography