title: Prognostic significance of histologic grading compared with subclassification of papillary thyroid carcinoma.
abstract: BACKGROUND
  Papillary thyroid carcinomas represent a diversity of morphologic subtypes and variants, but to the authors' knowledge the prognostic significance of subclassification is not clear. Therefore, the authors compared the value of histologic classification with a combined assessment of histologic key features such as marked nuclear atypia, tumor necrosis, and vascular invasion (i.e., histologic grade).
  
  
  METHODS
  One hundred twenty-eight surgically treated patients with papillary carcinoma > 10 mm were studied. The tumors were subclassified and individual histologic features were examined and compared in univariate and multivariate survival analyses.
  
  
  RESULTS
  Of all the cases, 55% were of the usual type, whereas 27% showed complex histologic features with different components present and 18% represented specific subtypes. Tall cell differentiation showed an increased frequency of tumor necrosis and vascular invasion, and tumors with solid areas had an increased occurrence of mitotic figures and vascular invasion. Patients with tall cell tumors tended to have reduced survival (P = 0.074), and two patients with columnar cell features died of the disease. When combined, the group of patients with all tumor subtypes had significantly reduced survival when compared with the remainder of patients (P = 0.034), although the difference was only minor. Histologic grade was highly significant (P = 0.0001) in survival analysis, together with mitotic frequency (P = 0.028), S-phase (P = 0.015), and G(2)M-phase fractions (P = 0.040). In multivariate analysis, tumor dimension (P = 0.019) and histologic grade (P = 0. 008) showed significant and independent prognostic importance, whereas subclassification was not found to be significant.
  
  
  CONCLUSIONS
  Subclassification of papillary thyroid carcinomas had only a minor prognostic impact, whereas histologic grade was a strong and independent prognostic marker. The authors recommend that all papillary carcinomas be given a histologic grade based on a combined examination of nuclear atypia, tumor necrosis, and vascular invasion. [See editorial on pages 1766-68, this issue.]
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania Health System, Philadelphia, PA, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Akslen
authors.forename: V A
authors.initials: VA
authors.lastname: LiVolsi
mesh_terms: D000328:Adult; D002291:Carcinoma, Papillary / Q000145:classification / Q000473:pathology*; D002467:Cell Nucleus / Q000648:ultrastructure; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D009367:Neoplasm Staging / Q000379:methods*; D009389:Neovascularization, Pathologic; D011379:Prognosis; D016019:Survival Analysis; D013964:Thyroid Neoplasms / Q000145:classification / Q000473:pathology*