title: Aggressive variants of papillary thyroid microcarcinoma are associated with extrathyroidal spread and lymph-node metastases: a population-level analysis.
abstract: BACKGROUND
  Tall cell variant (TCV) and diffuse sclerosing variant (DSV) of papillary thyroid cancer are aggressive subtypes, for which tumors ≤1 cm have not been exclusively studied.
  
  
  METHODS
  The SEER database (1988-2009) was used to compare characteristics of TCV ≤1 cm (mTCV) and DSV ≤1 cm (mDSV) with classic papillary thyroid microcarcinoma (mPTC). Survival was analyzed with the Kaplan-Meier method and log-rank test, and risk factors for nodal metastases with chi-square analysis and binary logistic regression.
  
  
  RESULTS
  There were 97 mTCV, 90 mDSV, and 18,260 mPTC patients. mTCV incidence increased by 79.9% (p=0.153) over the study period, while mDSV incidence decreased by 10.3% (p=0.315). Compared to classic mPTC, mTCV tended to be larger on average (7.1 mm vs. 5.3 mm, p<0.001), with higher rates of multifocality (47.2% vs. 34.0% respectively, p=0.018) and lymph-node examination (63.9% vs. 39.2% respectively, p<0.001), while in mDSV, nodal metastases were more frequent (57.1% vs. 33.1% respectively, p=0.007). Both aggressive variants had higher rates of extrathyroidal extension (27.8% mTCV vs. 13.3% mDSV vs. 6.1% mPTC, p<0.001). Aggressive variants also received radioactive iodine more frequently (39.2% mTCV vs. 40.0% mDSV vs. 29.1% mPTC, p<0.001). However, they were not statistically more likely to receive thyroidectomy over lobectomy compared to classic mPTC. There were no significant differences in overall and disease-specific survival between the histologies. In mTCV, after adjustment, extrathyroidal extension was independently associated with size >7 mm (odds ratio (OR) 4.4 [CI 1.5-13.6]) and nodal metastasis with multifocality (OR 5.4 [CI 1.3-23.4]) and extrathyroidal extension (OR 5.8 [CI 1.3-25.4]). No statistically significant predictors of extrathyroidal extension or nodal metastasis in mDSV were observed.
  
  
  CONCLUSIONS
  Aggressive variants of mPTC tend to exhibit more aggressive pathologic characteristics than classic mPTC, but survival appears to be similar. Treatment with total thyroidectomy and central lymphadenectomy may be warranted if the diagnosis can be made pre- or intraoperatively.
authors.affiliation: 1 Department of Surgery, Yale School of Medicine , New Haven, Connecticut.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Kuo
authors.forename: Paolo
authors.initials: P
authors.lastname: Goffredo
authors.forename: Julie A
authors.initials: JA
authors.lastname: Sosa
authors.forename: Sanziana A
authors.initials: SA
authors.lastname: Roman
mesh_terms: D000328:Adult; D018287:Carcinoma, Large Cell / Q000453:epidemiology / Q000473:pathology / Q000556:secondary* / Q000628:therapy; D002291:Carcinoma, Papillary / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000473:pathology / Q000556:secondary* / Q000628:therapy; D015331:Cohort Studies; D003131:Combined Modality Therapy; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use; D008207:Lymphatic Metastasis; D059351:Organ Sparing Treatments; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use; D011878:Radiotherapy; D018426:SEER Program; D012598:Sclerosis; D016019:Survival Analysis; D013961:Thyroid Gland / Q000000981:diagnostic imaging / Q000473:pathology* / Q000528:radiation effects / Q000601:surgery; D013964:Thyroid Neoplasms / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000473:pathology* / Q000628:therapy; D013965:Thyroidectomy; D014018:Tissue Distribution; D047368:Tumor Burden; D014481:United States / Q000453:epidemiology
chemical_list: D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals