title: Molecular imaging with (99m)Tc-MIBI and molecular testing for mutations in differentiating benign from malignant follicular neoplasm: a prospective comparison.
abstract: OBJECTIVE
  To compare mutation analysis of cytology specimens and (99m)Tc-MIBI thyroid scintigraphy for differentiating benign from malignant thyroid nodules in patients with a cytological reading of follicular neoplasm.
  
  
  METHODS
  Patients ≥18 years of age with a solitary hypofunctioning thyroid nodule (≥10 mm), normal thyrotropin and calcitonin levels, and a cytological diagnosis of follicular neoplasm were prospectively enrolled. Mutation analysis and (99m)Tc-MIBI scintigraphy were performed and patients were subsequently operated on to confirm or exclude a malignant lesion. Mutations for KRAS, HRAS and NRAS and for BRAF and translocations of PAX8/PPARγ, RET/PTC1 and RET/PTC3 were investigated. Static thyroid scintigraphic images were acquired 10 and 60 min after intravenous injection of 200 MBq of (99m)Tc-MIBI and visually assessed. Additionally, the MIBI washout index was calculated using a semiquantitative method.
  
  
  RESULTS
  In our series, 26 % of nodules with a follicular pattern on cytology were malignant with a prevalence of follicular carcinomas. (99m)Tc-MIBI scintigraphy was found to be significantly more accurate (positive likelihood ratio 4.56 for visual assessment and 12.35 for semiquantitative assessment) than mutation analysis (positive likelihood ratio 1.74). A negative (99m)Tc-MIBI scan reliably excluded malignancy.
  
  
  CONCLUSIONS
  In patients with a thyroid nodule cytologically diagnosed as a follicular proliferation, semiquantitative analysis of (99m)Tc-MIBI scintigraphy should be the preferred method for differentiating benign from malignant nodules. It is superior to molecular testing for the presence of differentiated thyroid cancer-associated mutations in fine-needle aspiration cytology sample material.
authors.affiliation: Department of Nuclear Medicine and Thyroid Centre, Oncology Institute of Southern Switzerland, Via Ospedale 12, 6500, Bellinzona, Switzerland. luca.giovanella@eoc.ch.
authors.forename: L
authors.initials: L
authors.lastname: Giovanella
authors.affiliation: Policlinico Universitario, Istituto di Medicina Nucleare, Messina, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Campenni
authors.affiliation: Department of Nuclear Medicine and Thyroid Centre, Oncology Institute of Southern Switzerland, Via Ospedale 12, 6500, Bellinzona, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Treglia
authors.affiliation: Department of Nuclear Medicine, RWTH University Hospital Aachen, Aachen, Germany.
authors.forename: F A
authors.initials: FA
authors.lastname: Verburg
authors.affiliation: Department of Nuclear Medicine and Thyroid Centre, Oncology Institute of Southern Switzerland, Via Ospedale 12, 6500, Bellinzona, Switzerland.|Ospedale Israelitico, Sezione di Endocrinologia e Diabetologia, Roma, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Trimboli
authors.affiliation: Department of Nuclear Medicine and Thyroid Centre, Oncology Institute of Southern Switzerland, Via Ospedale 12, 6500, Bellinzona, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Ceriani
authors.affiliation: Centre Hopitalier Universitaire Vaudouise, Institut de Pathologie, Lausanne, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Bongiovanni
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011446:Prospective Studies; D017256:Technetium Tc 99m Sestamibi; D000072637:Thyroid Epithelial Cells / Q000473:pathology*; D016606:Thyroid Nodule / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: D017256:Technetium Tc 99m Sestamibi
keywords: 99mTc-MIBI; Fine-needle aspiration cytology; Follicular neoplasms; Molecular markers; Mutation analysis; Scintigraphy; Thyroid